Tag Archives: bacteriophage

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.

Researchers successfully use viruses to clear years-old, antibiotic-resistant infection

Drug-resistant bacteria are a very concerning, and growing, threat. Now researchers at the Erasmus Hospital, Belgium, are working to recruit viruses in our fight against them.

Stylized bacteriophages. Image via Pixabay.

The researchers report successfully treating an adult woman, who was infected with drug-resistant bacteria, using a combination of antibiotics and bacteriophages (bacteria-killing viruses). Such experiments are the product of several decades’ worth of research into the use of bacteriophages in humans. The results are encouraging and could pave the way towards such viruses having a well-established role in the treatment of drug-resistant bacteria.

Viral helpers

The patient had been severely injured by the detonation of a bomb during a terrorist attack. She suffered multiple injuries, including one to her leg, that damaged it down to the bone. After surgery to have some of the tissue removed, she developed a bacterial infection on the leg. The bacteria responsible was Klebsiella pneumoniae, which is known to be resistant to antibiotics. It also creates biofilms that physically insulate affected areas from antibiotics.

Doctors tried to clear the infections, with no success, for several years. Left with no other options to try, her medical team suggested bacteriophage therapy, which they performed with assistance from researchers at the Eliava Institute in Tbilisi.

Bacteriophage therapy is not in medical use today as there are still concerns around the safety of using such viruses to treat humans with already-weakened immune systems, and many unknowns regarding when and how to best employ them.

To employ a bacteriophage in this role, one must be found that attacks the exact strain of bacteria that causes the infection. The researchers carried out a thorough search and testing process, and eventually found a suitable virus in a sample of sewer water. This was then isolated and grown in the lab, mixed into a liquid solution, and applied directly to the site of the infection. At the same time, the patient was put on a heavy antibacterial regimen.

Although it took three years of treatment, the patient is now free of the infection and able to walk again.

The team notes that their results showcase that such approaches can be effective treatment options when other avenues fail. However, they also explain that a better way of finding suitable bacteriophages must be developed before these interventions become viable in a practical sense. It simply takes too much time and effort to perform this search the same way the team did here for hospitals to realistically do this for multiple patients. There are currently no guarantees that a suitable virus will be found even if such a search is performed, as well.

The paper “Combination of pre-adapted bacteriophage therapy and antibiotics for treatment of fracture-related infection due to pandrug-resistant Klebsiella pneumoniae,” has been published in the journal Nature Communications.

Trained bacteriophages could help us with our drug resistance issues

Antibiotic-resistant bacteria are giving our medicine an increasingly-harder time. Bacteriophages however, viruses that prey on bacteria, could help us regain the upper hand.

A bacteriophage model made out of digital Lego blocks. Image credits Pascal / Flickr.

We’re quite spoiled in this modern day and age. Things as minor as cutting a finger are dealt with a wash, bandage, and an antibiotic at most — but they could be very deadly for our ancestors even 100 years ago. But as time passes, bacteria adapt to the drugs they’re exposed to, developing resistance.

It’s estimated that by 2050, antibiotic-resistant bacteria will claim over 10 million lives, as our existing therapies lose effectiveness and patients are left vulnerable.

Bacteria eaters

“Antibiotic resistance is inherently an evolutionary problem, so this paper describes a possible new solution as we run out of antibiotic drug options,” says Joshua Borin, lead author of the study. “Using bacterial viruses that can adapt and evolve to the host bacteria that we want them to infect and kill is an old idea that is being revived. It’s the idea of the enemy of our enemy is our friend.”

Bacteriophages, or phages for short, are viruses that specialize in infecting and reproducing using bacteria. They’re quite like the viruses that make us sick, only with a different ‘meal’ preference.

A new project led by researchers at the University of California San Diego, Biological Sciences department, have shown that phages can be trained, so to speak, to make them better able to attack and destroy bacteria. These pre-trained phages could help delay the onset of antibiotic resistance in groups of bacteria by physically destroying them (rather than chemically, as drugs do), and the team showcases this potential in their experiments. The study also included researchers at the University of Haifa in Israel and the University of Texas at Austin

The experiment was carried out in a series of unassuming laboratory flasks. Boiled down, it involved training specialized phages to recognize and attack certain bacterial strains, in preparation for a final ‘target’. The secret here is that the phages are given an opportunity to better adapt to their prey while kept in the flasks (through natural evolutionary processes). Phages that were ‘trained’ for 28 days, the team explains, were 1,000 times more efficient at suppressing the bacterial colony than untrained ones, and for between three to eight times as long.

“The trained phage had already experienced ways that the bacteria would try to dodge it,” said Associate Professor Justin Meyer, the study’s corresponding author. “It had ‘learned’ in a genetic sense. It had already evolved mutations to help it counteract those moves that the bacteria were taking. We are using phage’s own improvement algorithm, evolution by natural selection, to regain its therapeutic potential and solve the problem of bacteria evolving resistance to yet another therapy.”

While the findings are encouraging, they’re still quite preliminary — more of a proof of concept, if you will. Moving forward, the team wants to test their approach on strains of bacteria important in clinical settings, such as E. coli. Its viability as a treatment option will also be checked using animal models.

The paper “Coevolutionary phage training leads to greater bacterial suppression and delays the evolution of phage resistance” has been published in the journal PNAS.

New approach neutralizes influenza with modified bacteria predator membranes

A team of German researchers has developed a new way to deal with seasonal and avian influenza viruses. Their approach involves wrapping the pathogens in chemically-modified bacteriophage capsids, rendering them unable to infect human cells.

Electron micrograph of coliphages (a type of bacteriophage) attached to a bacterial cell. Image credits: Dr Graham Beards via Wikimedia.

The team hopes their work will help usher in new treatment options against such viruses. The method was tested in the lab with very encouraging results and is currently under investigation for possible applications against the coronavirus.

Viral straightjacket

“Pre-clinical trials show that we are able to render harmless both seasonal influenza viruses and avian flu viruses with our chemically modified phage shell,” explained Professor Dr. Christian Hackenberger, Head of the Department Chemical Biology at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) and Leibniz Humboldt Professor for Chemical Biology at HU Berlin. “It is a major success that offers entirely new perspectives for the development of innovative antiviral drugs.”

Current antiviral treatments only attack the influenza virus after it has infected our cells, the team reports, which is certainly useful — but preventing infection in the first place would be much more desirable and effective.

The trials — which used infected human lung tissue samples — showed that perfectly fitting a phage capsid onto these viruses can be used to neutralize their ability to infect lung cells. The capsid was specially developed by the team for this job, and works by binding itself to all the (hemagglutinin) proteins the virus can use to gain access through the membranes of human cells. During the infection process, these proteins bind to sugar molecules sprinkled through the membrane of lung tissue cells to allow entry. The core mechanism of this process, however, relies on the virus creating multiple bonds with a cell, rather than a single one.

Their quest to develop an inhibitor for these proteins started six years ago. The plan was to make such an inhibitor functionally resemble the membrane of a human lung cell. The team’s quest led them to the Q-beta phage, a harmless species of bacteriophage that lives in our intestines and usually preys on E.coli. The team removed and attached ligands (binders) to its casing — sugar molecules in this case — to act as bait binding sites for the virus’ proteins

“Our multivalent scaffold molecule is not infectious, and comprises 180 identical proteins that are spaced out exactly as the trivalent receptors of the hemagglutinin on the surface of the virus,” explained Dr. Daniel Lauster, a former Ph.D. student in the Group of Molecular Biophysics (HU) and now a postdoc at Freie Universität Berlin. “It therefore has the ideal starting conditions to deceive the influenza virus — or, to be more precise, to attach to it with a perfect spatial fit. In other words, we use a phage virus to disable the influenza virus!”

When samples of tissue infected with flu viruses were treated with the phage capsid, the influenza viruses were practically unable to reproduce. High-resolution cryo-electron microscopy and standard cryo-electron microscopy revealed that the modified capsids completely cover the viruses.

While definitely encouraging, the findings call for more preclinical studies to assess the method’s viability and safety for human use. We don’t yet know, for example, if the capsids themselves would elicit an immune response in mammals, and if such a response would enhance or impair their effect. And, of course, it has yet to be proven that the inhibitor is also effective in humans.

For now, the team is content to know that their approach has great potential and that it is “the first achievement of its kind in multivalency research,” according to Professor Hackenberger. The approach, he adds, is biodegradable, non-toxic, doesn’t cause an immune response in cell cultures, and is, at least in principle, applicable to other viruses and possibly even bacteria. The team is currently focusing on adapting it to the SARS-CoV-2 virus.

The paper “Phage capsid nanoparticles with defined ligand arrangement block influenza virus entry” has been published in the journal Nature Nanotechnology.

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.

Researcher finds new immune system in mucus

Think about mucus – what comes to mind? It’s slimy, it’s gross, no one really likes it, right? Well, as a team from San Diego State University showed, mucus is also home to a very powerful immune system that has the possibility to change the way doctors treat a number of diseases.

Bacteriophages are basically viruses that infect and replicates within bacteria. The research addressed all sorts of animals, from sea anemones to mice and humans, and found that bacteriophages adhere to the mucus of all of them. They placed bacteriophage on top of a layer of mucus-producing tissue and observed that the bacteriophage formed bonds with sugars within the mucus, adhering to its surface every single time.

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They then challenged them by injecting E. Coli in the mucus, and they found that the bacteriophage attacked and killed off the E. coli in the mucus, effectively forming an anti-microbial barrier protecting the host from infection and disease.

In order to test their discovery, they then conducted parallel research on non-mucus producing cells, infecting them with E. Coli, in the same fashion. The results were disastrous for the cells.

“Taking previous research into consideration, we are able to propose the Bacteriophage Adherence to Mucus — or BAM — is a new model of immunity, which emphasizes the important role bacteriophage play in protecting the body from invading pathogens,” Barr said.

But what makes this finding really special is that that the bacteriophage are already present on all humans and animals; they are recruited almost as mercenaries by cells who support them and then act as protectors to the host, attacking invaders on their own.

“The research could be applied to any mucosal surface,” Barr said. “We envision BAM influencing the prevention and treatment of mucosal infections seen in the gut and lungs, having applications for phage therapy and even directly interacting with the human immune system.”

Research paper.

The cholera bacteria.

Virus steals bacteria immune system and kills it

Researchers at Tufts University School of Medicine came across a particular strain of bacteriophage – a virus that infects and replicates within bacteria – that had stolen the functional immune system of the cholera bacteria.  The virus used the bacteria’s immune system against it to replicate and eventually kill the bacteria. The findings hint to the prospect of developing new phage therapies against bacterial diseases like cholera.

The cholera bacteria.

The cholera bacteria.

Until now, scientists have never witnessed this kind of behavior before which has prompted them to believe that phages – typically regarded as primitive particles of DNA or RNA – lack the necessary sophisticated mechanisms to develop an adaptive immune system, which is a system that can respond rapidly to a nearly infinite variety of new challenges.

Andrew Camilli, Ph.D., of Tufts University School of Medicine and also the lead author of the present study, came by the discovery by accident while analyzing DNA sequences of phages collected from stool samples of diseased cholera patients in Bangladesh.  It was then that he identified genes that expressed a functional immune system previously found only in some bacteria.

Each phage is parasitically mated to a specific type of bacteria, and the one for the cholera bacteria is called Vibrio cholerae. Surprised by the atypical genes in the virus, Camilli used phage lacking the adaptive immune system to infect a new strain of cholera bacteria that is naturally resistant to the phage. As expected, the phage failed to penetrate the bacteria, however, when the bacteria were infected with this new strain, the phage rapidly adapted and thus gained the ability to kill the cholera bacteria. This proves that the virus has the necessary tools to adapt and kill the bacteria.

“Virtually all bacteria can be infected by phages. About half of the world’s known bacteria have this adaptive immune system, called CRISPR/Cas, which is used primarily to provide immunity against phages. Although this immune system was commandeered by the phage, its origin remains unknown because the cholera bacterium itself currently lacks this system. What is really remarkable is that the immune system is being used by the phage to adapt to and overcome the defense systems of the cholera bacteria. Finding a CRISPR/Cas system in a phage shows that there is gene flow between the phage and bacteria even for something as large and complex as the genes for an adaptive immune system,” said Seed.

“The study lends credence to the controversial idea that viruses are living creatures, and bolsters the possibility of using phage therapy to treat bacterial infections, especially those that are resistant to antibiotic treatment,” said Camilli, professor of Molecular Biology & Microbiology at Tufts University School of Medicine and member of the Molecular Microbiology program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts University.

Phages have been found to be highly prevalent in stool samples infected with bacteria, and since a strain capable of hosting an adaptive immune system was encountered, it seems highly likely that it came naturally. The team is currently working on a study to understand precisely how the phage immune system disables the defense systems of the cholera bacteria, such that effective phage therapies might be developed.

The findings were reported in the journal Nature.

The best science pictures of 2010

With each passing year, science is becoming more and more visual,  and the pictures we get to see are more and more spectacular; from horror movie viruses, to nanolandscapes or computer simiulations, these are the winners of the 2010 Science and Engineering Visual Challenge.

The most detailed and advanced model of the HIV virus so far, it summarizes work from areas such as spectroscopy, genetics, virology and X-ray analysis

This is only a portion of AraNet, a gene association network from a plant that was built from over 50 million experimental observations. Each line here represents a link between two genes, and the colours represent how "hot" the connection is

This brilliant 3D illustration represents a bacteriophage virus brutally attacking a bacteria, such as E. Coli; after all, that's what bacteriophage do - they infect bacteria and then turn it into a virus factory

A computer generated model of a proposed structure for the yeast mitotic spindle developed during a two year project conducted by computer scientists, cell biologists, artists and physicists

Fungi make great foods, great beverages, and we find more and more uses for them every day. This splash illustrates their variety and how they influence our lives

77.6 billion people born, 969 million people killed - Everyone Ever in the world is a visual representation of the number of people who have lived vs people who have died in wars, massacres and genocides in recorded history.

This blue nanolandscape represents two molecules on a gold layer that form a self assembled layer, thus paving the way for self cleaning surfaces and not only

You would probably never guess it, but this is in fact the seed of a common tomato

Centipede milirobot

Seattle is one of the leading green cities, and they have also been leading a campaign for the smart tagging of garbage

Millions and millions of people use GPS each day, but little do they know that they handy tools rely on Einstein's theory of relativity to do their work...

A novel method to visualize vectors, where magnitude is shown by the color and the size of the glyphs, and the black and white represent the head and the tail of the vector