Tag Archives: antibiotic

Your microbiota will be having non-stop sex this Valentine’s Day

Even if you’re alone this Valentine’s Day, there’s no need to worry: some parts of your body will be getting plenty of action. In fact, your body will host a veritable carnival of the sensual in your tummy, as your microbiota will engage in an orgy of sex and swinger’s parties — where they’ll be swapping genes instead of keys.

A medical illustration of drug-resistant, Neisseria gonorrhoeae bacteria. Original image sourced from US Government department: Public Health Image Library, Centers for Disease Control and Prevention. Image in the public domain.

The salacious gene

Imagine you have a severe disease with a very unusual cure: you can treat by making love with someone who then passes on the necessary genes to cure your ailment. It is, as they say, sexual healing. Using sex to protect or heal themselves is precisely what bacteria can do, and it’s a crucial defense mechanism.

In the past, the research community thought bacterial sex (or conjugation, as scientists call it) was a terrible threat for humans, as this ancient process can spread DNA capable of conveying antibiotic resistance to their neighbors. Antibiotic resistance is one of the most pressing health challenges the world is facing, being projected to cause 10 million deaths a year by 2050.

But there’s more to this bacterial sex than meets the eye. Recently, scientists from the University of Illinois at Urbana-Champaign and the University of California Riverside witnessed gut microbes sharing the ability to acquire a life-saving nutrient with one another through bacterial sex. UCR microbiologist and study lead Patrick Degnan says:

“We’re excited about this study because it shows that this process isn’t only for antibiotic resistance. The horizontal gene exchange among microbes is likely used for anything that increases their ability to survive, including sharing vitamin B12.”

For well over 200-years, researchers have known that bacteria reproduce using fission, where one cell halves to produce two genetically identical daughter cells. However, in 1946, Joshua Lederberg and Edward Tatum discovered bacteria could exchange genes through conjugation, an entirely separate act from reproduction.

Conjugation occurs when a donor and a recipient bacteria sidle up to each other, upon which the donor creates a tube, called a pilus that attaches to the recipient and pulls the two cells together. A small parcel of DNA is then passed from the donor to the recipient, providing new genetic information through horizontal transfer.

Ironically, it wasn’t until Lederberg met and fell in love with his wife, Esther Lederberg, that they made progress regarding bacterial sex.

Widely acknowledged as a pioneer of bacterial genetics, Esther still struggled for recognition despite identifying the horizontal transfer of antibiotic resistance and viruses, which kill bacteria known as bacteriophages. She discovered these phages after noticing small objects nibbling at the edges of her bacterial colonies. Going downstream to find out how they got there, she found these viral interlopers hiding dormant amongst bacterial chromosomes after being transferred by microbes during sex.

Later work found that environmental stresses such as illness activated these viruses to replicate within their hosts and kill them. Still, scientists assumed that bacterial sex was purely a defense mechanism.

Esther Ledeberg in her Stanford lab. Image credits: Esther Lederberg.

Promiscuity means longevity

The newly-published study builds on Esther’s work. The study authors felt this bacterial process extended beyond antibiotic resistance. So they started by investigating how vitamin B12 was getting into gut microbial cells, where the cells had previously been unable to extract this vitamin from their environment — which was puzzling as, without vitamin B12, most types of living cells cannot function. Therefore, many questions remained about how these organisms survived without the machinery to extract this resource from the intestine.

The new study in Cell Reports uses the Bacteroidetes species, which comprise up to 80% of the human microbiome in the intestines, where they break down complex carbohydrates for energy.

“The big, long molecules from sweet potatoes, beans, whole grains, and vegetables would pass through our bodies entirely without these bacteria. They break those down so we can get energy from them,” the team explained.

This bacteria was placed in lab dishes mixing those that could extract B12 from the stomach with some that couldn’t. The team then watched in awe while the bacteria formed their sex pilus to transfer genes enabling the extraction of B12. After the experiment, researchers examined the total genetic material of the recipient microbe and found it had incorporated an extra band of DNA from the donor.

Among living mice, something similar happens. When the group-administered two different subgroups of Bacteroidetes to a mouse – one that possessed the genes for transferring B12 and another that didn’t — they found the genes had ‘jumped’ to the receiving donee after five to nine days.

“In a given organism, we can see bands of DNA that are like fingerprints. The recipients of the B12 transporters had an extra band showing the new DNA they got from a donor,” Degnan said.

Remarkably, the team also noted that different species of phages were also transferred during conjugation, exhibiting bacterial subgroup specificity in some cases. These viruses also showed the capacity to alter the genomic sequence of its bacterial host, with the power to promote or demote the life of its microbic vessel when activated.

Sexual activity in our intestines keeps us healthy

Interestingly, the authors note they could not observe conjugation in all subgroups of the Bacteroidetes species, suggesting this could be due to growth factors in the intestine or a possible subgroup barrier within this large species group slowing the process down.

Despite this, Degnan states, “We’re excited about this study because it shows that this process isn’t only for antibiotic resistance.” And that “The horizontal gene exchange among microbes is likely used for anything that increases their ability to survive, including sharing [genes for the transport of] vitamin B12.”

Meaning that bacterial sex doesn’t just occur when microbes are under attack; it happens all the time. And it’s probably part of what keeps the microbiome and, by extension, ourselves fit and healthy.

New compounds fight drug-resistant bacteria by turning their membranes into prison cells

Two new antibiotic compounds join the fight against drug-resistant bacteria.

Staphylococcus aureus seen under the electron microscope.
Image credits Mogana Das Murtey, Patchamuthu Ramasamy.

The compounds have been named corbomycin and complestatin, and are part of the glycopeptide family of antibiotics produced by soil bacteria (the Actinomycetes family in particular). The unique way in which they attack bacteria makes them very promising candidates against drug-resistant infections, the study reports.

Don’t tear down this wall

The study reports that laboratory studies on mice showed that these two substances interact with bacteria in a completely different way from anything we’ve seen before.

“Bacteria have a wall around the outside of their cells that gives them shape and is a source of strength,” said study first author Beth Culp, a PhD candidate in biochemistry and biomedical sciences at McMaster.

“Antibiotics like penicillin kill bacteria by preventing building of the wall, but the antibiotics that we found actually work by doing the opposite — they prevent the wall from being broken down. This is critical for cell to divide.”

Both corbomycin and complestatin have proven themselves effective in combating Methicillin-resistant Staphylococcus aureus (MRSA), a family of bacteria that is highly resistant to antibiotics and is responsible for many serious, potentially life-threatening infections today.

Glycopeptides inhibit the growth of cell membranes by blocking the synthesis of peptidoglycan, which is a vital building block. It may not sound like much of a hassle but this effectively prevents bacteria from multiplying, as they need to generate extra membrane before dividing. These two compounds essentially ensures the bacteria are “trapped in a prison, and can’t expand or grow.”

For the study, the team started with a list of known glycopeptides — a chemical class that includes some of the most powerful and dangerous antibiotics humanity has ever wielded — and the microbial genes that encode their synthesis. They hoped that compounds encoded in different genes would also engage bacteria in different ways. This step set them on the trail of corbomycin and complestatin.

Looking at the family tree of known members of the glycopeptides, researchers studied the genes of those lacking known resistance mechanisms, with the idea they may be antibiotics demonstrating a different way to attack bacteria. Further testing in collaboration with Yves Brun and his team from the Université de Montréal carried out with cell imaging equipment, revealed how they acted on bacterial membranes.

“This approach can be applied to other antibiotics and help us discover new ones with different mechanisms of action,” Culp explains. “We found one completely new antibiotic in this study, but since then, we’ve found a few others in the same family that have this same new mechanism.”

One of the most exciting findings of the study is that the compounds show efficiency even against Enterococcus strains resistant to vancomycin and S. aureus strains that show an intermediate resistance to vancomycin. Vancomycin is used as a last-line-of-defense antibiotic against gram-positive infections that do not respond to any other treatment.

The paper “Evolution-guided discovery of antibiotics that inhibit peptidoglycan remodelling” has been published in the journal Nature.

New shape-shifting metal particles shred drug-resistant bacteria to bits

New research at RMIT University is looking into liquid metals as a solution to drug-resistant bacteria.

Image credits Aaron Elbourne et al., (2020), ACS Nano.

The approach the team is working on involves using magnetic particles of liquid metals to physically destroy bacteria, side-stepping the use of antibiotics entirely. The study describes how this technique can be used to destroy both bacteria and bacterial biofilms — protective, layered structures that house bacteria — without harming human cells.

A shred of hope

“We’re heading to a post-antibiotic future, where common bacterial infections, minor injuries and routine surgeries could once again become deadly,” says Dr Aaron Elbourne, a Postdoctoral Fellow in the Nanobiotechnology Laboratory at RMIT, and the paper’s lead author.

“It’s not enough to reduce antibiotic use, we need to completely rethink how we fight bacterial infections.”

The rising levels of antibiotic resistance recorded throughout the world is a very scary development, one that we’ll have to tackle sooner rather than later. Modern antibiotics fundamentally changed the rules of life for us when they were first developed 90 years ago. Before that, any infection was basically the luck of the draw: even a routine medical intervention or the most unassuming of wounds could become infected, and even the humblest infection could kill.

They still can, but modern antibiotics offer us a level of protection that people in the past could only pray for. Still, overuse and misuse of these compounds are forcing pathogens to adapt and survive, and they’re doing so much faster than we can develop new, more powerful drugs. It’s estimated that antibiotic-resistant bacteria cause in excess of 700,000 deaths per year, a figure which could reach 10 million a year by 2050 (which would make it deadlier than cancer). Bacteria’s ability to form biofilms further complicates the matter, as such structures render them virtually immune to all existing antibiotics.

Antibiotics are chemical compounds that prevent bacteria from functioning properly. They can do this through a range of methods: by blocking their ability to form proteins, by breaking down their membrane, or by interfering with their ability to reproduce. Human cells and bacterial cells are similar but different enough that antibiotics can be made to target the latter and leave the former unaffected.

The team wanted to develop a whole new method to attack pathogens, one that does away completely with chemical means (which bacteria can adapt to).

“Bacteria are incredibly adaptable and over time they develop defences to the chemicals used in antibiotics, but they have no way of dealing with a physical attack,” Dr. Elbourne explains.

“Our method uses precision-engineered liquid metals to physically rip bacteria to shreds and smash through the biofilm where bacteria live and multiply.”

The team’s approach involves the use of nano-sized droplets of liquid metal. When exposed to a low-intensity magnetic field, these droplets change shape and grow sharp edges.

To check how effective they would be at the task, the team placed droplets in contact with a bacterial biofilm then made them change shape. The sharp edges broke down the biofilm and physically ruptured the bacterial cells inside, the team found. They proved effective against both Gram-positive and Gram-negative bacterial biofilms. After 90 minutes of exposure to the particles, both biofilms were destroyed and 99% of the bacteria inside were killed, the team explains, suggesting that they would be effective as a wide-range treatment option. Human cells were left unaffected by the nanoparticles.

The team says that their method is versatile enough to be used in multiple settings and approaches. For example, a coating of the nanoparticles could be sprayed on implants to help prevent infections for hip or knee replacements. They also plan to explore its effectiveness against fungal infections, cancerous tumors, and build-ups such as cholesterol plaques.

“There’s also potential to develop this into an injectable treatment that could be used at the site of infection,” said Dr Vi Khanh, a Postdoctoral Research Fellow at the North Carolina State University and co-author of the paper.

The nanoparticles are currently undergoing preclinical trials in animals. If all goes well, human trials could start in a few years.

The paper “Antibacterial Liquid Metals: Biofilm Treatment via Magnetic Activation” has been published in the journal ACS Nano.

Immune cells on our skin destroy drug-resistant bacteria (MRSA) all the time, study finds

A new study from Karolinska Institutet found that methicillin-resistant Staphylococcus aureus (MRSA) bacteria are kept in check, on our skin, by a type of immune cell known as a neutrophil.

MRSA bacteria.
Image credits Public Health Image Library (PHIL).

The findings can help explain why some people only carry the superbug for short periods without contracting an infection.

“The skin is an incredibly dynamic biological environment where immune cells and microbes stand-off against one another to maintain some kind of equilibrium, a fraught peace,” says Keira Melican, senior researcher at the Department of Neuroscience, Karolinska Institutet, who led the study.

“Breaks in these equilibria typically lead to bad outcomes for humans, and understanding how this process works on the skin could have an impact on how we prevent and treat skin infection in the future.”

The authors developed a “humanized” mouse model by grafting human skin onto mice — this helped them look at how human tissues would respond in vivo. After colonizing the skin with MRSA, they explain, neutrophils were recruited to the skin, where they destroyed the antibiotic-resistant bacteria.

While the experiment sounds a bit… cruel, it was designed this way to address the main limitation of animal models as proxies for humans: their biology is different from ours on many (if not all) levels. The team needed to incorporate human tissues into the model animal to get a more accurate representation of how a human body would react to the bacteria.

So why go through all this trouble? Staphylococcus aureus is a very common species of bacteria: up to 30% of all humans carry it long-term, at any given time, generally in the upper respiratory tract and on the skin. It’s generally not very damaging or deadly, although it can cause some skin infections or food poisoning among a few other problems.

However, and this is a big however, several strains of S. aureus are rapidly becoming resistant to most (sometimes all) our antibiotic courses, especially in hospital settings. Known as MRSA, infections with such strains are life-threatening and very difficult to treat. The new study aims to find new ways of containing or combating MRSA by understanding how our natural immune response helps keep it at bay.

“We hope that our humanised skin model will help make sure that our results are relevant to humans, and not just mice,” says Melican.

The paper “Neutrophil recruitment to noninvasive MRSA at the stratum corneum of human skin mediates transient colonization” has been published in the journal Cell Reports.

Gut bacteria resistance to antibiotics doubles in the last 20 years

Researchers have uncovered a worrisome trend in which harmful bacteria known to cause dangerous stomach diseases are becoming increasingly resistant to even some of the most powerful antibiotics at our disposal. According to a new study, resistance to commonly-used antibiotics has doubled in the past 20 years.

Credit: Wikimedia Commons.

For their study, the team led by Francis Megraud, Professor of Bacteriology at the University of Bordeaux in France and the founder of the European Helicobacter & Microbiota Study Group, studied the antibiotic response of 1,232 patients from 18 countries who were infected with Helicobacter pylori (H. pylori).

If left untreated, this bacterial infection may cause gastric ulcers, lymphoma, and even gastric cancer.

For years, doctors have been prescribing clarithromycin to ward off H. pylori, but since 1998, resistance to the antibiotic has surged from 9.9% to 21.6% as of last year. The researchers found similar jumps in resistance for levofloxacin and metronidazole.

H. pylori infection is already a complex condition to treat, requiring a combination of medications. With resistance rates to commonly used antibiotics such as clarithromycin increasing at an alarming rate of nearly 1% per year, treatment options for H. pylori will become progressively limited and ineffective if novel treatment strategies remain undeveloped. The reduced efficacy of current therapies could maintain the high incidence rates of gastric cancer and other conditions such as peptic ulcer disease, if drug resistance continues to increase at this pace,” Megraud said in a statement.

The study found that the highest rates of clarithromycin resistance in H. pylori were in Southern Italy (39.9%), Croatia (34.6) and Greece (30%). It’s no wonder that these countries are also known for overconsumption of antibiotics in inappropriate situations, including for conditions like cold and flu (for which antibiotics are useless since they’re caused by viral infections). These countries also have poor antibiotic resistance containment strategies.

Antibiotic resistance occurs when an antibiotic is no longer effective at controlling or killing bacterial growth. Bacteria that are ‘resistant’ can multiply in the presence of various therapeutic levels of an antibiotic. Sometimes, increasing the dose of an antibiotic can help tackle a more severe infection but in some instances — and these are becoming more and more frequent — no dose seems to control bacterial growth. Each year, 25,000 patients from the EU and 63,000 patients from the USA die because of hospital-acquired bacterial infections which are resistant to multidrug-action. 

According to a 2013 CDC report titled “Antibiotic Resistance Threats in the United States, antibiotic resistance is responsible for $20 billion in direct health-care costs in the United States. Without urgent action, the number of infections could rise dramatically.

H. pylori is believed to be present in about one half of the world’s population, but most never get sick. Some, however, aren’t so lucky and the bacteria can cause some uncomfortable complications like inflammation of the stomach lining (gastritis) and peptic ulcers.

For some time, H. pylori antibiotic resistance has been considered as a severe threat to public health, with the World Health Organization (WHO) calling clarithromycin-resistant H. pylori a high priority for antibiotic research and development. According to an OECD report, superbug infections could cost the lives of around 2.4 million people in Europe, North America and Australia over the next 30 years. The good news is three out of four deaths could be averted by spending just 2 USD per person a year on measures like handwashing and more prudent prescription of antibiotics.

“The findings of this study are certainly concerning, as H. pylori is the main cause of peptic disease and gastric cancer,” commented Mário Dinis-Ribeiro, President of the European Society of Gastrointestinal Endoscopy. “The increasing resistance of H. pylori to a number of commonly-used antibiotics may jeopardize prevention strategies.”

The findings appeared in the journal UEG Journal and were presented today at UEG Week Barcelona 2019.

Tower Bridge.

London’s waterways found to contain antibiotic-resistant bacterial genes

London’s waterways are rife with antibiotic resistant genes.

Tower Bridge.

Image via Pixabay.

The Regent’s Canal, Regent’s Park Pond, and the Serpentine contained high level of antibiotic resistance genes, a new study reports, but none were worse than the Thames. These genes encode resistance to common antibiotics such as penicillin, erythromycin, and tetracycline. They found their way into the water from bacteria in human and animal waste.

Laced waters

“This [study] shows that more research is needed into the efficiency of different water treatment methods for antibiotic removal, as none of the treatments currently used were designed to incorporate this,” says lead author Dr. Lena Ciric from UCL Civil, Environmental and Geomatic Engineering.

“This is particularly important in the case of water bodies into which we discharge our treated wastewater, which currently still contains antibiotics. It is also important to look into the levels of antibiotics and resistant bacteria in our drinking water sources.”

When humans or animals take antibiotics, part of the active substance gets excreted (while still active) into sewer systems and, from there, into freshwater sources. Once there, they’re exposed to bacteria and create an environment that favors resistant microbes. These will multiply faster than their non-resistant counterparts, making the resistance genes more prevalent in the total population. Resistant microbes can also share their resistance with their peers via lateral gene transfer.

The team developed a DNA-analysis method that can be used to measure the quantity of fourteen types of antibiotic resistance genes per liter of water. They then applied it in different water systems throughout London and compared the results. The Thames River had the highest level of antibiotic resistance genes, followed by The Regent’s Canal, Regent’s Park Pond, and the Serpentine. Antibiotics entering the sewer system are diluted through flushing, but even low levels can encourage resistance genes to multiply and spread to more microbes. The Thames is likely to have higher levels of antibiotics and resistant genes because a large number of wastewater treatment works discharge into it both upstream and in London.

The authors note that there is currently no legislation in place which specifies that antibiotics or the genes that encode their resistance need to be scrubbed from water sources. This could mean that antibiotics and said genes could be present in small amounts in drinking water, although this would require testing.

The team is now working on finding a way to remove antibiotics, resistant bacteria, and antibiotic-resistance genes from London’s natural water system using slow sand filtration, which is a form of drinking water treatment. This technique is already in use around the world including at Thames’ Coppermills Water Treatment Works, they explain, which provides drinking water for most of north east London. Their plan is to beef-up this filtration technique by tweaking the properties of the sand and activated carbon used in the filters, and by varying water flow rates.

The paper ” Use of synthesized double-stranded gene fragments as qPCR standards for the quantification of antibiotic resistance genes” has been published in the journal Journal of Microbiological Methods.


Use of antibiotics without a prescription is an understudied but serious issue in the US

Antibiotic use without a prescription is a “prevalent public health problem” in the US, according to a new metastudy.


Image via Pixabay.

The use of antibiotics without a doctor’s prescription is an understudied but “prevalent” problem in the US, according to researchers from Baylor College of Medicine and the Center for Innovations in Quality, Effectiveness, and Safety. The team carried out a review of 31 previously-published studies on the topic to determine how frequent such use of antibiotics is in the US, and to examine the factors that lead to such usage of antibiotics.

Casually antibiotic

“Nonprescription antibiotic use is clearly a public health problem in all racial/ethnic groups, but many aspects are understudied,” the authors write. “The need to focus on nonprescription antibiotic use in community-based antimicrobial stewardship programs is urgent.”

The team, led by Larissa Grigoryan, M.D., Ph.D., from the Baylor College of Medicine in Houston, started with a body of 17,422 studies which they screened down (for relevance to this topic and other inclusion criteria) to 31. From these studies, the team report that nonprescription antibiotic use varies from 1% (among people who regularly visit a clinic when needed) to 66%, which was reported among Latino migrant workers. Another study found that around one quarter of its participants intended to use antibiotics without a prescription.

These antibiotics were sourced through various avenues, from saving leftover prescriptions, getting them from friends and family, or obtaining them from local markets “under the counter,” the authors explain. Findings from a scoping review are published in Annals of Internal Medicine. Anywhere from 14% to 48% of people — depending on population characteristics — store antibiotics for future use.

People turn to nonpescription use of antibiotics mainly due to lack of insurance or health care access, because they can’t afford the cost of a physician visit or prescription, due to embarrassment about seeking care for a sexually transmitted infection, or from not being able to get time off of work to visit a clinic or physician’s office, among several other reasons.

“In 2013, the U.S. Centers for Disease Control and Prevention (CDC) estimated that each year, 2 million infections caused by antimicrobial-resistant pathogens occur in the United States, resulting in 23,000 deaths,” Dr. Ayo Moses, a family physician with CareMount Medical in New York, told Healthline.

One of the main risks to public health regarding the nonprescription use of antibiotics has to do with the rise of bacterial antibiotic resistance. According to the European Antibiotic Awareness Day website, “if we take antibiotics repeatedly and improperly, we contribute to the increase in antibiotic-resistant bacteria, one of the world’s most pressing health problems,” adding that “if at some point in time you, your children or other family members need antibiotics, they may no longer work,” and that nonprescription use of antibiotics “is not a responsible use of antibiotics”.

On a personal level — if you’re don’t consider drug-resistant diseases a personal threat, that is — taking antibiotics isn’t guaranteed to make you feel better, and may actually cause side-effects. Antibiotics only work against bacteria, not against viruses, so diseases such as colds and flu will be totally unaffected. Taking antibiotics will not reduce the severity of your symptoms and will not help you feel better faster, while other over-the-counter medicine can. Taking antibiotics without a doctor’s supervision can even cause an infection to become more powerful.

On top of that, it’s important to keep in mind that any antibiotics you may stockpile can lose potency quickly — meaning they might not work anyway by the time you get to use them. So don’t rely on it!

The paper “Use of Antibiotics Without a Prescription in the U.S. Population” has been published in the journal Annals of Internal Medicine.

Kitchen Sponge.

Phages in kitchen sponges could help us wipe antibiotic resistant bacteria clean off

New student research from the New York Institute of Technology (NYIT) could help us stem the tide of antibiotic-resistant infections — using your kitchen sponge.

Kitchen Sponge.

The savior we didn’t want, but the one we need.
Image credits Hans Braxmeier.

Research at the NYIT has zoomed in on bacteriophages — viruses that infect bacteria — living in our kitchen sponges. These biological particles, often shorthanded as ‘phages’, may prove useful in fighting antibiotic-resistant bacteria, the team reports.

Spongy science

“Our study illustrates the value in searching any microbial environment that could harbor potentially useful phages,” said Brianna Weiss, a Life Sciences student at New York Institute of Technology.

Kitchen sponges aren’t exactly the cleanest items in your house. In fact, it’s exposed to all kinds of different microbes every day and is pretty much crawling with a microbiome of bacteria. And where there are bacteria, there are also bacteriophages, viruses that target, infect, and multiply on the back of bacteria.

Students in a research class at NYIT isolated bacteria from their own used kitchen sponges and then used them as bait to see which phages could attack them. Two of the students successfully baited phage strains that could infect these bacteria. The team then decided to ‘swap’ these two phage strains and check whether they could cross-infect the bacteria isolated by the other student — and it turned out they could. The phage strains successfully infected and then killed bacteria recovered from the other sponge.

“This led us to wonder if the bacteria strains were coincidentally the same, even though they came from two different sponges,” said Weiss.

To get to the bottom of things, the team isolated and compared the DNA of these bacterial strains. They report that both belong to the Enterobacteriaceae family, a vast grouping of rod-shaped bacteria that are commonly found in feces. Some members of the Enterobacteriaceae family have been recorded to cause infections in hospital settings. Although related, the researchers do add that lab analysis revealed chemical variations between the two strains.

“These differences are important in understanding the range of bacteria that a phage can infect, which is also key to determining its ability to treat specific antibiotic-resistant infections,” said Weiss.

“Continuing our work, we hope to isolate and characterize more phages that can infect bacteria from a variety of microbial ecosystems, where some of these phages might be used to treat antibiotic-resistant bacterial infections.”

The project fits into a larger drive to develop non-chemical avenues of fighting bacteria. Such measures are meant, on the one hand, to reduce the incidence and spread of antibiotic resistance in bacterial strains by limiting exposure to such drugs. On the other hand, they aim to give us a functioning defense against strains that have already acquired partial or (much worse) complete immunity to our antibiotics. Some of these ideas that we’ve looked at in the past include laying down antibacterialspike pits‘, shredding them with polymers and nanomaterials, using (Komodo) dragon blood, and straight-up causing some bacterial civil war.

Still, the World Health Organization is concerned that, despite drug-resistant bacteria being “one of the biggest challenges mankind has to face in the near, as well as distant future,” and despite these strains claiming hundreds of thousands of lives every year, the world is simply not prepared to deal with the threat. “Only 34 out of 133 questioned countries have even a basic plan to combat the misuse of antibiotics fuelling drug resistance,” Andrei reported at the time.

Hopefully, research such as the one we’re discussing today will mature before our antibiotics become powerless in the face of bacteria. We’re simply over-relying on antibiotics, a study published last May explained, and methods such as the use of phages could help us break the pattern before it is too late.

The findings have been presented at ASM Microbe, the annual meeting of the American Society for Microbiology.

Escherichia Coli.

Researchers film bacteria sharing antibiotic resistance in real time — and find a potential fix

New research into how antibiotic resistance spreads among bacterial populations points the way forward to fighting this growing threat.

Escherichia Coli.

Escherichia Coli.
Image credits Gerd Altmann.

Growing levels of antibiotic resistance, both in scope and sheer effectiveness, is a very real threat for us. It’s easy, in this day and age, to consider most bacteria and the diseases they cause as simple nuisances. But that safety is owed to the antibiotics and active compounds we’ve developed to protect us — should they turn ineffective, we’re as much at the mercy of these germs as any other organism on the planet.

However, new research shows it isn’t unstoppable. Robust, yes; backed-up with redundancy systems, yes — but not unstoppable.

The tiny pump that could

The research was carried out by a team of researchers from the Université Lyon and CNRS, the French National Center for Scientific Research. They successfully filmed the process of antibiotic resistance acquisition in real time, thus finding a new and central player that takes part in this process.

Antibiotic resistance primarily spreads among bacteria through a process known as (bacterial) conjugation, which is basically the sharing of genetic material. Systematic genetic sequencing of both pathogenic and environmental strains of bacteria suggests that a very wide range of genetic elements can be shared via conjugation which encodes resistance to most or all of the antibiotic classes currently in use.

So we know how it goes down, but we’re still in the dark in regards to how long it takes for conjugation to work its magic and how antibiotics interfere with the process. That’s what the present research aimed to find out.

The team worked with a strain of Escherichia Coli (E.coli) bacteria resistant to tetracycline, a commonly used antibiotic. Tetracycline works by attaching itself to the bacteria’s molecular mechanisms, rendering them unable to produce proteins. The team exposed the bacteria to tetracycline in the presence of another strain that was not resistant to the substance. Previous research told the team that, in such conditions, the spread of antibiotic resistance hinges on the first strain clearing the drug out using “efflux pumps” on their membrane before it can wreak havoc internally, thus conferring them some degree of resistance to the drug.

The team reports seeing DNA transmission being carried out between individuals of the two strains with one specific efflux pump, the TetA pump. Using fluorescent marking and live-cell microscopy, the researchers tracked the spread the DNA encoding this pump from resistant bacteria and how the recipient ones expressed the genes.

It only took 1 to 2 hours for the single-stranded DNA fragments put out by the efflux pumps to be turned into a double-stranded DNA molecule and, subsequently, into a functional protein, they report. In effect, that is the timeframe required for resistance to spread between different strains of bacteria. You can see the process in the video below; green bacteria are the donors (i.e. resistant E.coli strain) and the red ones are the recipients. In effect, everything you see turning green is learning tetracycline resistance from its peers.


Given the way tetracycline works — by blocking the production of proteins — you’d reasonably expect it to block the ‘red’ bacteria from synthesizing TetA efflux pumps (they’re made of proteins). However, the team is surprised to report that this isn’t the case. Paradoxically, the bacteria were able to survive and develop a resistance to tetracycline even in the presence of this drug — which suggested there’s another, unknown factor at work here.

It seems to be another efflux pump, they explain. Called AcrAB-TolC (scientists are good with naming stuff), this pump is present in virtually all bacteria, but serves a general role. As such, it’s less efficient than TetA at ejecting tetracycline, but it is still able to remove a small quantity from the cell, allowing the bacteria to carry out a minimal level of protein synthesis. This process allows bacteria to become durably resistant to antibiotics should they be provided with the right genes from the environment.

However, the findings also point the way to a potential fix for acquired antibiotic resistance.

“We could even consider a therapy combining an antibiotic and a molecule able to inhibit this generalist pump,” says Christian Lesterlin, a researcher at Lyon’s Molecular Microbiology and Structural Biochemistry laboratory and the paper’s corresponding author.

“While it is still too soon to envisage the therapeutic application of such an inhibitor, numerous studies are currently being performed in this area given the possibility of reducing antibiotic resistance and preventing its spread to the various bacterial species.”

The paper “Role of AcrAB-TolC multidrug efflux pump in drug-resistance acquisition by plasmid transfer” has been published in the journal Science.

Medicinal plants used in the Civil War can stomp our modern antibiotic-resistant germs

New research into old germ-fighting methods suggests they could prove effective in combating antibiotic-resistant bacteria today.


Bronze statue of Abraham Lincoln in Virginia, USA.
Image credits Dennis Larsen

At the height of the Civil War, the paper reports, the Confederate Surgeon General released a guide of traditional plant remedies from the South that battlefield physicians could draw upon when faced with shortages of conventional medicine. Three of the plants in this guide — white oak (Quercus alba), tulip poplar (Liriodendron tulipifera), and devil’s walking stick (Aralia spinosa) — have antiseptic properties that could be useful today, the authors explain.

The seeds of salvation

“Our findings suggest that the use of these topical therapies may have saved some limbs, and maybe even lives, during the Civil War,” says Cassandra Quave, senior author of the paper and assistant professor at Emory’s Center for the Study of Human Health and the School of Medicine’s Department of Dermatology.

The team found that extracts from these three plants have significant antimicrobial properties in the face of three dangerous species of multi-drug-resistant bacteria: Acinetobacter baumannii, Staphylococcus aureus, and Klebsiella pneumoniae. These bacteria are often seen in wound-associated infections.

Quave’s research focuses on understanding the role of plants in traditional healing and other practices, a field known as ethnobotany.

“Ethnobotany is essentially the science of survival—how people get by when limited to what’s available in their immediate environment,” she says. “The Civil War guide to plant remedies is a great example of that.”

“Our research might one day benefit modern wound care, if we can identify which compounds are responsible for the antimicrobial activity,” adds Micah Dettweiler, the first author of the paper.

If the active ingredients in these plants are identified, explains co-author Daniel Zurawski from the Wound Infections Department at the Walter Reed Army Institute of Research, they can be tested through modern “models of bacterial infection.” In a way, he says, this is mixing the “wisdom of our ancestors” with modern techniques to create new solutions for the problems we’re facing today.

Around 1 in 13 soldiers that lived through the Civil War went back home with missing limbs, the authors report. “Far more Civil War soldiers died from disease than in battle,” Zurawski explains, adding that he was surprised to see how “common amputation was as a medical treatment for an infected wound.” At the time, germ theory was still crude, and very much a work-in-progress. The training medical personnel at the time received was also shoddy at best.

An antiseptic was simply defined as a tonic used to prevent “mortification of the flesh.” Iodine and bromine were sometimes used to treat infections, according to the National Museum of Civil War Medicine, although the reason for their effectiveness was unknown. Other conventional medicines available at the time included quinine for treating malaria, and morphine and chloroform to block pain.

Union blockade

The Confederacy, however, didn’t have reliable access to these compounds. In the 1863 copy of “Resources of the Southern Fields and Forests,” Francis Peyre Porcher (who was commissioned by the Confederacy for this task) set about detailing alternatives to the essential but lacking medicine. Porcher was a botanist and surgeon from South Carolina, and his book represents a compilation of medicinal plants of the Southern states, including plant remedies used by Native Americans and enslaved Africans. Among others, the book contains a description of 37 species for treating gangrene and other infections. His work formed the foundation upon which Samuel Moore, the Confederate Surgeon General, produced the “Standard supply table of the indigenous remedies for field service and the sick in general hospitals.”

The team collected samples of the three plants from around their university’s campus, abiding to the specifications Porcher set out in his book. Extracts were produced from white oak bark and galls; tulip poplar leaves, root inner bark and branch bark; and the devil’s walking stick leaves, and were then tested on multi-drug-resistant bacteria commonly found in wound infections.

White oak and tulip poplar extracts inhibited the growth of S. aureus, while the white oak extracts also inhibited the growth of A. baumannii and K. pneumoniae, the team writes. Extracts from both of these plants also inhibited S. aureus from forming biofilms, which can insulate it against antibiotics.

Staphylococcus aureus is considered the most dangerous of the staph bacteria, and can spread from skin infections or medical devices to infect internal organs. Klebsiella pneumoniae is a leading cause of hospital infection and can result in life-threatening cases of pneumonia and septic shock. Aceinetobacter baumannii is particularly worrisome as it exhibits extensive resistance to most first-line antibiotics, and is closely associated with combat wounds. Extracts from the devil’s walking stick inhibited both biofilm formation and quorum sensing — a signaling system that staph bacteria use to manufacture toxins — in S. aureus.

“There are many more ways to help cure infections, and we need to focus on them in the era of drug-resistant bacteria,” says Quave.

“Plants have a great wealth of chemical diversity, which is one more reason to protect natural environments,” Dettweiler adds.

The paper “American Civil War plant medicines inhibit growth, biofilm formation, and quorum sensing by multidrug-resistant bacteria” has been published in the journal Nature Scientific Reports.


Study proposes five new rules to prevent antibiotic resistance “disaster”

Efforts to fight antibiotic resistance aren’t “nearly radical enough” today, according to a new study.


Image credits Emilian Danaila.

Relying too much on reducing antibiotic use and implementing new drugs could lead to “disaster”, says Dr. Ben Raymond, of the University of Exeter. In a new study, Dr. Raymond proposes five rules for the “sustainable use” of antibiotics which would help us maintain the efficiency of this class of drugs and prevent antibiotic resistance from becoming a deadly problem.

Resistance fighters

“People think the best way to tackle antibiotic resistance is to give out fewer antibiotics and find new drugs. Those are important steps, but this approach alone is not nearly radical enough,” says Dr. Raymond, of the Centre for Ecology and Conversation on the University of Exeter’s Penryn Campus in Cornwall.

“Even if we can keep finding new drugs, disaster will follow if we use them in the same way as we use current ones. No drug yet discovered is evolution proof, and the typical practice of using single drugs at once, in unprotected ‘monotherapies’ is unsustainable.”

What he proposes instead is a multi-pronged approach intended to prevent what the World Health Organisation calls “a post-antibiotic era in which common infections and minor injuries can once again kill.” The measures include taking steps to protect new drugs before resistance becomes a problem, diversifying the range of antimicrobials currently in use to avoid relying too much on a handful of drugs (which also speeds up the evolution of resistance for those drugs), and using data to design management plans for particular superbugs.

“This ‘business as usual’ approach can be disastrous, as exemplified by the history of resistance in gonorrhoea and the emergence of untreatable infections,” Dr. Raymond explains. “Resistance to new antibiotics can become widespread in two or three years, so new drugs must be partnered with more sustainable patterns of use.”

The five ‘rules’ outlined in the study are:

  1. Prevention. Echoing the old adage, Dr. Raymond wisely notes that “resistance is easier to deal with before it becomes severe.” Avoiding heavy use of single drugs for extended periods of time creates less evolutionary pressure for its active compound (i.e. bugs have less need and opportunities opportunity to develop resistance to a particular compound, as they don’t see it that frequently).
  2. Don’t rely on “fitness costs.” Some approaches call for break periods in the use of a particular drug, in the hope that bacteria resistant to it will die off to their competition because they carry resistance genes that are no longer useful (i.e. genetic dead weight.) While the idea behind the approach can work, resistance to a drug does not necessarily vanish because of an interruption in the use of a drug.
  3. Limit bacteria’s ability to mutate drug-resistance genes. One approach is to use antibiotic cocktails, as microbes rarely develop resistance to multiple antibiotics at once. Slowly building a massive reservoir of antibiotic-resistance genes in the wild is “madness” according to Dr. Raymond. Traces of antibiotics in wastewater, or the use of antibiotics in livestock farming, are doing exactly that. “As an individual you are very unlikely to have acquired an antibiotic resistant microbe from an animal, but it’s highly likely that environmental contamination has helped some of the microbes in your body acquire resistance,” he says.
  4. Low doses don’t work, but short courses might. A greater pool of mutations can give microbes the chance to resist low doses of antibiotics, so lowering the dose doesn’t prevent resistance from evolving. However a shorter, more intense course of treatment might benefit patients without giving the bugs a chance to evolve, he says.
  5. Know your enemy. “If you don’t know what kind of resistance is around among patients or in your hospital, you could give people the wrong drug at the wrong time,” he says. “The more data you have, the better you can design your resistance management programmes. Resistance management programmes should target specific microbes or groups of microbes, rather than resistance in general.”

“Some humility in the face of natural selection can ensure that human creativity keeps pace with evolutionary innovation,” he adds, noting that other disciplines have a broader knowledge of resistance management, but that their input is “not widely appreciated” among microbiologists.

The paper “Five rules for resistance management in the antibiotic apocalypse, a road map for integrated microbial management” has been published in the journal Evolutionary Applications.

Butterfly in a jar.

Researchers develop way to trap and study bacteria so we can fight disease and antibiotic resistance

New research from the University of York (UoY) will allow us to capture and study individual bacteria — hundreds of them at a time.

Butterfly in a jar.

The secret is to trap them!
Image credits Isabel Perelló.

When scientists want to see how a certain strain of bacteria will react to a given drug, they’ll flood a culture with different levels of the compound and see what happens. For the most part, this is a pretty effective technique and tells us what we need to know — does drug A kill bacterium Q, for example?

However, this approach has its own limitations. A novel method detailed in a new study wants to address these limitations by allowing researchers to look at individual bacteria rather than whole populations.

I’m not like the other bacteria

“Individual bacteria behave differently from one another and so looking at them as one large group can mean that inaccurate assumptions are made. This can lead to delayed or prolonged treatment regimes,” says Giampaolo Pitruzzello, a PhD student from the UoY’s Department of Physics and lead author of the study.

“We wanted a method that allowed clinical decisions to be made faster and more accurately. This meant finding a way of trapping individual bacteria and testing multiple features at once, rather than growing large cultures in a dish.”

Knowing how individual bacteria react to certain drugs could help doctors pick the right antibiotic for the right infection more quickly, reducing treatment times. This would also reduce the risk of complications developing before or during treatment (as the bacteria can be dealt with sooner, before they have a chance to run amok) and nip the rise of antibiotic resistance in the bud (as we can ensure that most if not all of these bugs die off).

Compared to current methods — which rely on growing whole cultures, billions of organisms strong — which take about 24-48 hours to run a full test, the team’s method can analyze bacterial susceptibility to certain drugs within a single hour. Even better, the team showed that their method can be used to look at hundreds of individual bacteria at the same time. As a proof of concept, they analyzed the shape and swimming ability of multiple bacteria and how different drugs interfere with their function.

The most effective drugs, they report, are those that messed up an organism’s shape and ability to move at the same time. The team explains that, while they chose to look at these two traits in particular, the method can be used to analyze virtually any property of bacteria.

“This method would allow clinicians to prescribe effective, targeted antibiotics early on in an infection which would lead to improved clinical outcomes whilst reducing overall levels of antibiotic use,” says Professor Thomas Krauss, from the UoY’s Department of Physics, who led the research efforts. “The aim is to get the right drug, to the right patient, at the right time.”

So how do they do it? Well, the team basically created a bacteria trap. They used very narrow channels filled with fluids and made bacteria swim along their length. The channels fed into microscopic traps where bacteria would come to a halt. Once there, the team injected different drugs into each trap and placed the bacteria under the microscope to see how they fared.

The approach yielded very encouraging results in a lab setting, and the team now hopes to expand their testing to include clinical samples (those taken directly from patients). Ultimately, they hope to refine the technique so it can be used in medical settings, such as clinics and hospitals, where it can save actual lives.

“This new technique offers a quick result so we can target more precisely which antibiotic to use to get patients better quicker,” explains Dr Adrian Evans, co-author and specialist in Urogynaecology at York Hospital. “This may well help reduce the burden of sepsis in our communities, which is an ever-increasing problem.”

The paper “Multiparameter antibiotic resistance detection based on hydrodynamic trapping of individual E. coli” has been published in the journal Lab on a Chip.


Treated wastewater could release antibiotic-resistance genes into the wild



Image credits Iva Balk.

These compounds end up in the water supply, potentially driving the spread of antibiotic resistance.

A team from the University of Southern California Viterbi School of Engineering say that even low concentrations of a single type of antibiotic can lead to the spread of resistance to multiple classes of these drugs in the wild. The team reports that antibiotics present in wastewater plants are a key driver of such resistance in the wild.

Drug dumping

“We’re quickly getting to a scary place that’s called a “post-antibiotic world,” where we can no longer fight infections with antibiotics anymore because microbes have adapted to be resilient against those antibiotics,” said Adam Smith, assistant professor of civil and environmental engineering at USC and lead investigator of the study. “Unfortunately, engineered water treatment systems end up being sort of a hot-bed for antibiotic resistance.”

While most of the antibiotics we ingest get metabolized (broken down) inside our bodies, small amounts find their way into urine and end up in wastewater treatment plants. So far, so good.

The problem starts inside these plants, the team explains. One of the most common ways in which wastewater is treated is through a membrane bioreactor, a process that relies on filtration systems and bacteria to remove and break down waste products. While doing their job, some of these bacteria encounter those trace-levels of antibiotics. They either die upon exposure or adapt to become (more) resistant to the compounds.

Those that do adapt pass their genes off to later generations — or to their neighbors via horizontal gene transfer.

One of the more dire possible scenarios, the team writes, is for these antibiotic-resistant bacteria (or free-floating bits of their DNA) to make it through the filtration membrane, into waterways, eventually reaching the ocean. Treated wastewater is also sometimes recycled for use in irrigation, car washes, firefighting, or to replenish groundwater supplies — so these bacteria could reach human populations directly.

The team believes that the amount of antibiotic-resistant organisms in treatment plants could be reduced through alterations in the treatment processes. For example, the use of anaerobic (oxygen free) processes rather than aerobic processes, or more aggressive filtration, could help limit their development. The team tested a small-scale anaerobic membrane bioreactor and compared the resulting antibiotic-resistant populations to those in treatment plants and their effluents for different types of antibiotics.

They report that these profiles are different in the treatment plants and effluents, and therefore one cannot be used to predict the other. However, they also found that there wasn’t a clear-cut correlation between the antibiotics they introduced into the system and the resulting resistance — they found bacteria with genes allowing for resistance to multiple classes of antibiotics, although only one such compound was tested at a time.

“The multi-drug resistance does seem to be the most alarming impact of this,” Smith said. “Regardless of the influent antibiotics, whether it’s just one or really low concentrations, there’s likely a lot of multi-drug resistance that’s spreading.”

This is probably generated by gene elements called plasmids, which can carry resistance genes for several types of antibiotics at a time. Because of their extremely small size — 1,000 times smaller than bacteria — plasmids can easily make it through filtration systems in the treatment process and reach the environment. Needless to say, that would not be good.

The paper “Evaluating Antibiotic Resistance Gene Correlations with Antibiotic Exposure Conditions in Anaerobic Membrane Bioreactors” has been published in the journal Environmental Science & Technology.

Staphylococcus epidermidis biofilm.

One bacteria lives on everybody’s skin — and it’s becoming resistant to antibiotics

Researchers at the University of Bath, UK, report that an extremely common bacterium is developing antibiotic resistance.

Staphylococcus epidermidis biofilm.

A Staphylococcus epidermidis biofilm formed on a titanium substrate.

MRSA, E. coli, they’re all very scary. But new research says there’s a newcomer to the Scary Table: Staphylococcus epidermidis, a widespread species that lives on our skins. A close relative of MRSA, this bacteria is a leading cause of infections (some of them life-threatening) following surgery.

It’s abundant, widespread, generally overlooked — and rapidly becoming resistant to antibiotics, warn researchers at the Milner Centre for Evolution at the University of Bath.

Staphil-oh no no no.

The team says we should take the threat posed by S. epidermidis much more seriously than we do today. They recommend taking extra precautions especially in the case of patients with heightened risk of infection that are due to undergo surgery.

The researchers started by retrieving samples of the bacteria from patients who developed infections following following hip replacement, knee joint replacement, and fracture fixation operations. Then, they compared the genetic material of these strains with those in swab samples harvested from the skin of healthy volunteers.

They report identifying a set of 61 genes that allow some strains of S. epidermidis to cause life-threatening infection. These genes help the bacterium grow in the bloodstream, avoid the host’s immune response, make the cell surface sticky so that the organisms can form biofilms, and make the bug resistant to antibiotics, they write. This finding, the team hopes, will further our understanding of why some strains can become infectious — in the future, this should help us keep the risk of post-surgery infection with S. epidermidis at bay.

The team also found that a small number of (healthy) individuals carry a much more deadly strain of the bacteria on their skin. Determining which strain (relatively harmless, dangerous, or one of these very dangerous ones) a potential patient carries on their skin before surgery would help doctors prepare extra hygiene precautions as needed.

“[S. epidermidis has] always been ignored clinically because it’s frequently been assumed that it was a contaminant in lab samples or it was simply accepted as a known risk of surgery,” says  Professor Sam Sheppard, Director of Bioinformatics at the Milner Centre for Evolution at the University of Bath and the study’s lead author. “Post-surgical infections can be incredibly serious and can be fatal. Infection accounts for almost a third of deaths in the UK so I believe we should be doing more to reduce the risk if we possibly can.

“Because the bug is so abundant, they can evolve very fast by swapping genes with each other,” he explains. “If we do nothing to control this, there’s a risk that these disease-causing genes could spread more widely, meaning post-operative infections that are resistant to antibiotics could become even more common.”

The paper “Disease-associated genotypes of the commensal skin bacterium Staphylococcus epidermidis” has been published in the journal Nature Communications.

International Space Station.

Antibiotic-resistant bacteria found on the ISS — they’ve been up there for at least two years

That the ISS is laden with germs isn’t, honestly, much of a surprise. But some of them are highly resistant to antibiotics, and that’s worrying.

International Space Station.

The International Space Station as seen on May 2010.
Image credits NASA / Crew of STS-132.

The International Space Station might sound spacey-clean but it is, in fact, crawling with microbes. JPL-NASA scientists report identifying several strains of Enterobacter in samples collected from the space station’s toilet and exercise area. Enterobacter is best known for infecting patients with weakened immune systems in hospitals, and being extremely resistant to antibiotics.


Luckily, the strains identified on the ISS aren’t pathogenic to (they don’t infect) humans. And, while it’s virtually impossible to have humans without bacteria — we trail our own microbiomes around anywhere we go — just finding any strain of Enterobacter on the station is enough cause for concern.

The genus is infamous for its preying on immunocompromised patients here on Earth; it’s also renowned for its ridiculous resistance to antibiotics. Space is (pardon the quip) an environment out of this world. There’s more radiation, there’s virtually no gravity, there are humans everywhere, crammed up in a tube with a lot of their carbon dioxide. All of these constraints could alter how the microbes live and multiply — these changes, could, in turn, cause them to become pathogenic to humans.

NASA employs quite a handful of microbiologists at its Jet Propulsion Laboratory, who regularly analyze microbe samples sent down from the ISS to see whether space life alters their populations or habits. The microbiologists also keep an eye on any potential biological hazards to either equipment or the astronauts’ health. This is the first time they’ve identified antibiotic-resistant Enterobacter strains in the station.

“To show which species of the bacteria were present on the ISS, we used various methods to characterise their genomes in detail. We revealed that genomes of the five ISS Enterobacter strains were genetically most similar to three strains newly found on Earth,” explained microbiologist Kasthuri Venkateswaran.

“These three strains belonged to one species of the bacteria, called Enterobacter bugandensis, which had been found to cause disease in neonates and a compromised patient, who were admitted to three different hospitals (in east Africa, Washington state and Colorado).”

The samples were collected in 2015. Since no astronauts have been struck down since then, the bugs seem not to be an immediate threat. However, the team says this state of affairs can quickly change — and it would be bad. The space-borne Enterobacter were found to be resistant to a wide range of antibiotics, and virtually completely immune to cefazolin, cefoxitin, oxacillin, penicillin, and rifampin.

Enterobacter cloacae.

Enterobacter cloacae.
Image credits CDC Public Health Image Library (PHIL #6552).

The strains also share 112 genes with clinical strains, associated with virulence, disease, and defense. The team reports that computer models show a 79% probability that the space strains will develop a human pathogen and cause disease.

Right now, however, the astronauts are safe. The possibilities, however worrying, have yet to be tested in living organisms. So the team is working to better understand the situation and develop a response procedure (that they hope never to use) against these bacteria.

“Whether or not an opportunistic pathogen like E. bugandensis causes disease and how much of a threat it is, depends on a variety of factors, including environmental ones,” Venkateswaran said. “Further in vivo studies are needed to discern the impact that conditions on the ISS, such as microgravity, other space, and spacecraft-related factors, may have on pathogenicity and virulence.”

The paper “Multi-drug resistant Enterobacter bugandensis species isolated from the International Space Station and comparative genomic analyses with human pathogenic strains” has been published in the journal BMC Microbiology.

E.coli rendering.

Some bacteria can ‘hibernate’ through antibiotic treatments, new paper finds

When antibiotics come knocking, bacteria may simply sleep the threat away.

E.coli rendering.

Digital rendering of E.coli bacteria.
Image via Fotolia.

Researchers from the University of Copenhagen report that pathogenic bacteria have a surprising defensive tactic against antibiotics: hibernation. The research might help us fight antibiotic-resistant infections.

Nap it out

Almost all types of pathogenic bacteria eventually develop strains that are tolerant of or resistant to antibiotic treatments. This is particularly problematic as the fraction of bacteria which survive treatment — although tiny — can later multiply, maintaining infection in the face of our antibiotic efforts.

However, a small number of bacterial species do away with this mechanism completely, yet still retain the ability to resist the drugs meant to kill them. In an effort to understand why, the Copenhagen team turned to E. coli.

“We studied E. coli bacteria from urinary tract infections that had been treated with antibiotics and were supposedly under control,” says Professor Kenn Gerdes of the University of Copenhagen’s Department of Biology, paper co-author.

“In time, the bacteria re-awoke and began to spread once again,” he explains

The team found that a few individuals in the overall bacterial population ‘hid’ from the antibiotics in a dormant, hibernation-like state. The bugs slept through the treatment, and only resumed their regular activity once the dangerous compounds were removed.

Antibiotics generally work by attacking a bacteria cell’s ability to grow — so these hibernating individuals are virtually immune to their effects.

“A bacterium in hibernation is not resistant. It is temporarily tolerant because it stops growing, which allows it to survive the effects of an antibiotic,” says Professor Gerdes.

Hibernating bacteria seem to share the same genetic characteristics as all other individuals in a given population, the team reports. So, as of right now, they can’t say exactly why some members enter a dormant state while their peers do not. The team did, however, identify an enzyme in dormant individuals that governs the ‘hibernation’ process. A compound that could interfere with this enzyme’s functioning, or its synthesis, could help to keep these bacteria from becoming invulnerable to antibiotics.

“The discovery of this enzyme is a good foundation for the future development of a substance capable of combating dormant bacteria cells,” says Professor Gerdes.

“The enzyme triggers a ‘survival program’ that almost all disease-causing bacteria deploy to survive in the wild and resist antibiotics in the body. Developing an antibiotic that targets this general programme would be a major advance,” he adds.

Although the findings are encouraging, it will still be several years before they can be turned into a safe and useable treatment, the team writes.

The paper “The kinases HipA and HipA7 phosphorylate different substrate pools in Escherichia coli to promote multidrug tolerance” has been published in the journal Science Signaling.

Combining antibiotics may be more effective, new study suggests

The traditional belief is that combining two or more antibiotics yields diminishing returns. But a new study suggests that this might not always be the case. Instead, scientists argue, there are thousands of viable combinations.

In a world where germs are becoming more and more drug-resistant, doctors and physicians need all the help they can get. While designing new drugs and limiting existing resistance are essential, scientists are also trying to get as much as possible out of existing resources. With this in mind, a team of researchers tried to see whether the conventional approach of using just one antibiotic is always the correct way to go, or if there are more efficient alternatives.

“There is a tradition of using just one drug, maybe two,” said Pamela Yeh, one of the study’s senior authors and a UCLA assistant professor of ecology and evolutionary biology. “We’re offering an alternative that looks very promising. We shouldn’t limit ourselves to just single drugs or two-drug combinations in our medical toolbox. We expect several of these combinations, or more, will work much better than existing antibiotics.”

Working with 8 different antibiotics, they analyzed every possible four and five-drug combination, varying the dosage in different ratios, ending up with a total of 18,278 combinations in all. They tested out all these combinations on E. coli, a common type of bacteria that can live in our intestines.

They were expecting a few fringe combinations to be very effective at killing the bacteria, but they were surprised to see just how many effective combinations they discovered. Among the 4-drug combinations, there were 1,676 groupings that performed better than expected, while in the 5-drug combinations, 6443 groupings did better than expected.

“I was blown away by how many effective combinations there are as we increased the number of drugs,” said Van Savage, the study’s other senior author and a UCLA professor of ecology and evolutionary biology and of biomathematics. “People may think they know how drug combinations will interact, but they really don’t.”

The key to this success might lie in the way different antibiotics target pathogens.

“Some drugs attack the cell walls, others attack the DNA inside,” Savage said. “It’s like attacking a castle or fortress. Combining different methods of attacking may be more effective than just a single approach.”

Of course, this doesn’t necessarily mean that antibiotic combinations should become the new norm. There are still many things that need to be accounted for, both in terms of different pathogens and how different treatments would work on different people. But the study suggests that at least in some cases, combinations could be useful — and efficient.

Researchers are currently creating open-access software based on their results, in order to help other researchers and clinicians further develop this approach. It’s certainly a thing worth looking into more, and it’s something that one day could very well change the way antibiotics are administered

Researchers have figured out how some soil bacteria turn antibiotic drugs into food. Credit: Michael Worful.

Some bacteria eat antibiotics — and this might actually be a good thing

Researchers have figured out how some soil bacteria turn antibiotic drugs into food. Credit: Michael Worful.

Researchers have figured out how some soil bacteria turn antibiotic drugs into food. Credit: Michael Worful.

You might have heard all about how many bacterial strains are becoming resistant to even our strongest antibiotics. The most immediate (and frightening) consequence is that humanity risks reverting to a dark age of medicine where unstoppable infectious diseases spread like wildfire. What’s truly mindboggling is that not only have some strains become resistant to antibiotics, they’ve learned to embrace them, consuming them for food.

Researchers at the Washington University School of Medicine in St. Louis have investigated what freaky biology allows bacteria to ingest as food what would normally be poison for them. Writing in the journal Nature Chemical Biologythe authors say that three distinct set of genes become active in trials when the bacteria ate penicillin but stayed inactive while the bacteria ate sugar.

The researchers worked with four distinct species of soil bacteria. These species likely gained antibiotic resistance due to the unregulated dumping of antibiotic-laden waste into local waterways, which also ends up in the soil. Because bacteria easily share genetic material, the antibiotic-resistant genes quickly spread through the community.

Each of the three genes identified by the researchers corresponds to one of three steps the bacteria take in order to consume antibiotics as food. First, the bacteria neutralize the dangerous part of the antibiotic which is toxic to them. With the toxin disarmed, the bacteria are then free to consume the matter which is essentially just like any other carbon-based food at this point.

“Ten years ago we stumbled onto the fact that bacteria can eat antibiotics, and everyone was shocked by it,” said senior author Gautam Dantas in a statement. “But now it’s beginning to make sense. It’s just carbon, and wherever there’s carbon, somebody will figure out how to eat it. Now that we understand how these bacteria do it, we can start thinking of ways to use this ability to get rid of antibiotics where they are causing harm.”

Antibiotic resistance is no joke. Whenever bacteria survive an antibiotic onslaught, it can acquire resistant through mutation of the genetic material or by ‘borrowing’ pieces of DNA that code for the resistance to antibiotics from other bacteria, like those from livestock. Moreover, the DNA that codes the resistance is grouped in an easily transferable package which enables the germs to become resistant to many antimicrobial agents.

In a previous long-form article, I wrote:

“Before Alexander Fleming discovered penicillin in 1928, there was no effective treatment for infections such as pneumonia, gonorrhea or rheumatic fever. Fleming’s discovery kicked off a golden age of antimicrobial research with many pharmaceutical companies developing new drugs that would save countless lives. Some doctors in the 1940s would famously prophesize that antibiotics would finally eradicate the infectious diseases that had plagued humankind throughout history. Almost a hundred years later since Fleming made his milestone discovery not only are bacterial infections still common, the misuse and overuse of antibiotics are threatening to undo all of this medical progress.”

According to the CDC, the following bacterial strains have developed the most resistance such that they’ve been listed as urgent hazards:

  • Clostridium difficile. Causes severe diarrhea, especially in older people and those who have serious illnesses.
  • Enterobacteriaceae. These normally live in the digestive tract but can invade other parts of the body, like the urinary tract, and cause infections.
  • Neisseria gonorrhoeae. Causes gonorrhea, a sexually transmitted infection. In 2016, the WHO said gonorrhea might soon become untreatable. 

However, although antibiotic-munching bacteria sound terrifying, the authors of the new study say their adapted abilities could be exploited in our favor. One of the reasons so many bacteria develop resistance in the first place is due to poor waste management. In China and India — the world’s most important producers of pharmaceuticals — it’s common practice for waste leftover from the antibiotic manufacturing process to end up in waterways. So, why not use the antibiotic-resistant bacteria to clean up such dumps? That would be one primary application of the recent findings.

“Of course, the benefits of any such bioremediation program would need to be weighed against the risk of releasing a genetically modified bacterium into the environment and the potential spread of antibiotic resistance/degradation genes to other organisms,” the authors wrote.

“Before starting this project, we already knew that a lot of bacteria in the soil could eat antibiotics, and we all would have been very surprised if it had turned out they were somehow doing this without using antibiotic resistance genes in some way. So I think that it is mostly good news that, while resistance is part of this pathway, we now have the blueprints for how bacteria eat an antibiotic. We actually used this knowledge to design a benign strain of laboratory E. coli to do an even better job eating penicillin,” Terence Crofts, first author of the new paper and a researcher at the University of Washington, told ZME Science.

One major challenge is that the soil bacteria capable of eating antibiotics are difficult to work with and the rate at which they consume the drugs is far too slow to make an impact. The researchers, however, are confident that they can engineer E. coli, which is a well-studied bacteria and a far more tractable species, for this purpose. In experiments, the Washington University researchers showed that they could give E. coli antibiotic-eating abilities, allowing it to thrive on penicillin. The bacteria usually requires sugar to survive, but due to genetic modifications and the presence of a key protein, the E. coli survived on a sugar-free diet of penicillin.

“I think an important take-away from this paper is how we look at antibiotics. We (humans) see antibiotics just as a medicine we get from the clinic, but most of our antibiotics are actually chemicals that are made by or based on compounds that soil bacteria and fungi use to compete against their neighbors. So from the point of view of soil microbes, antibiotics are just another type of carbon-based molecule that while sometimes toxic are fair game for eating if they can be detoxified. When we consider antibiotics as being by and for bacteria, it makes sense that antibiotic resistance and antibiotic degradation/eating are widespread in the soil,” Crofts concluded.

Petri dish.

New method developed to stop bacteria from sharing antibiotic resistance genes

The molecular mechanisms underpinning the spread of drug resistance in bacteria populations have been identified — and a new class of molecules has been designed to fight it.

Petri dish.

Image credits via Pixnio.

The rise of multi-drug resistant bacteria is often — and to my mind, as well as the WHO’s — rightly held to be one of the biggest current threats to global health. A large part of what constitutes this threat is that bacteria can share resistance among themselves — like IT guys swapping USB sticks with new firewall software, bacteria can share genes encoding antibiotic resistance.

In a bid to nip this growing threat in the bud, researchers at the European Molecular Biology Laboratory (EMBL) have uncovered and then unraveled one of the major resistance-transfer mechanisms. They’ve also developed proof-of-concept molecules to carry out this bacterial sabotage.

Resisting the resistance

Over time, bacteria have developed a certain resistance level to most drugs we use today. The worst are arguably those that have developed resistance to multiple classes of antibiotics; examples range from MRSA (methicillin-resistant Staphylococcus aureus), VRE (vancomycin-resistant enterococcus), and ESBL (extended spectrum beta-lactamase) producing Enterobacteriaceae.

One of the major drivers of resistance spread throughout bacterial populations are transposons. Also called ‘jumping DNA’, they are bits of genetic code that can autonomously move throughout the genome. When this movement occurs between bacteria, it spreads antibiotic resistance genes among individuals. Very bad for us.

Under the leadership of Orsolya Barabas, one research team at the EMBL became the first to determine the structure of a crystal-like, protein-DNA structure which inserts these transposons in recipient bacteria. Dubbed the transposase protein, this molecule could hold the key to throwing the whole process into disarray.

Protein structure.

The unusual shape of the transposase protein (blue) forces the transposon DNA (grey) to unwind and open up.
Image credits Cell.

The protein has an unusual shape, which allows it to bind to DNA in an inactive state, keeping the transposon safe from potential chemical or physical damage until it’s delivered to its new host. Its shape also forces the transposon DNA to unwind, the team notes, allowing the protein to insert these genes into a wide array of locations within the genomes of many different bacteria.

“If you think of ropes or wires, they are usually bundled and wound-up to make them stronger. If you want to tear or cut one, it’s much easier if you unwind and loosen it first,” says EMBL group leader Orsolya Barabas, who led the work.

“It’s the same for DNA, and the transposon transfer mechanism takes advantage of this.”

Because the transposase protein first unwinds and separates the transposon’s strands, they can more readily be cut and pasted to a new site in the recipient genome. Again, very bad for us.

Luckily, Barabas’ team used the protein’s crystal structure to develop molecules that should block the transposons’ movement through two mechanisms. The first prevents the transposase protein from activating by blocking its architecture with a newly designed peptide, a short chain of amino acids — in other words, it wedges itself in the transposase so that it can’t unfurl and deliver the DNA cargo.

The second method ‘corrupts’ the genetic data. This molecule, a DNA-mimic, binds to the transposon and blocks the DNA strand replacement in the host; no replacement, no resistance transfer.

“As we believe these features are broadly present in these jumping DNA elements, but not in related cellular systems, they may be quite specific to transposons. This way, we can target only the bacteria we want, and not the many good bacteria in our bodies and the environment,” Barabas explains.

The molecules are still far from trials with living hosts. For now, Barabas and her colleagues will focus on better understanding the transfer mechanisms, as well as on developing and testing new strategies to block it.

The paper “Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance” has been published in the journal Cell.


Small populations of bacteria can elude antibiotics — here’s how we’re fixing that

Small populations of bacteria respond differently to antibiotics than larger ones, a new study reports — offering clues as to why it’s so hard to kill these bugs off.


Image via Pixabay.

A population of bacteria that sports 100 or fewer cells doesn’t play by the rules; at least, not as far as antibiotics are concerned. Larger populations tend to respond homogeneously throughout their members, but with small populations, even antibiotics are more of a hail mary, new research shows — sometimes they work, sometimes they don’t, and it seems to be completely down to chance.

Strength in (small) numbers

Which, understandably, is not an ideal state of affairs for us hairless bipeds. Especially because for decades, the prevailing wisdom held that reducing the number of bacteria down to a few hundred individuals would be enough for the immune system to come in and carry the day.

“More recently, it became clear that small populations of bacteria really matter in the course of an infection,” says lead author Minsu Kim.

“The infectious dose — the number of bacterial cells needed to initiate an infection — turned out to be a few or tens of cells for some species of bacteria and, for others, as low as one cell.”

The researchers wanted to understand why antibiotic treatments sometimes work, and sometimes fail. They’ve started with the usual culprits: variations in immune responses between people, or possible mutations of bacteria that make them more virulent in some cases. Kim, however, wasn’t impressed. She suspected that something else was at work here, and her suspicions only became stronger when researchers working with model organism C. elegans recorded unexpected treatment failures even for antibiotic-susceptible infections.

Focusing their research only on small populations of bacteria, the team discovered that their interaction with antibiotics is based on a different dynamic than that of large populations. The researchers observed that antibiotics induce fluctuations in the density of bacterial populations as they kill off individuals, which they expected; however, they also noted that when the population’s rate of growth overcame the rate at which the antibiotics killed individuals, clearance failed.

Armed with this knowledge, they created a low-dose cocktail of drugs to preempt this quirky dynamic. This mix contained a bactericide (a compound that kills bacteria) and bacteriostat (a substance that slows the growth of bacteria). Taken together, these were intended to limit the random fluctuation seen by the team, and thus make it more probable to keep the population’s overall death rate higher than the growth rate. They then took this cocktail to the lab to see how it works. First, they showed that it was effective on a small population of drug-susceptible E. coli. Then they applied it to a clinically-isolated strand of antibiotic resistant E. coli — again, the cocktail worked.

“We’ve shown that there may be nothing special about bacterial cells that aren’t killed by drug therapy — they survive by random chance,” said Kim. “This randomness is a double-edged sword. On the surface, it makes it more difficult to predict a treatment outcome. But we found a way to manipulate this inherent randomness in a way that clears a small population of bacteria with 100 percent probability.”

“By tuning the growth and death rate of bacteria cells, you can clear small populations of even antibiotic-resistant bacteria using low antibiotic concentrations.”

The team hopes that their model cocktail can help guide development of more refined antibiotic treatment courses. Their end goal is to help researchers develop treatments that use lower doses to kill an infection entirely, for as many different infections as possible.

“It’s important because if you treat a bacterial infection and fail to kill it entirely, that can contribute to antibiotic resistance,” says Kim.

Not all antibiotics available today fit the model they’ve developed, however. More research is needed get this approach ready for use in a clinical setting.

Antibiotic resistance is a huge and growing problem. Essentially, it means that at some point in the future our drugs won’t be able to reliably protect against bacteria — or they could become useless against them altogether. Antibiotic resistance could lead to 10 million people dying each year by 2050, a total health care burden of $100 trillion, and a reduction of 2% to 3.5% in world Gross Domestic Product (GDP) by the same year.

The paper “Antibiotic-induced population fluctuations and stochastic clearance of bacteria” has been published in the journal eLife.