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superbugs vs antibiotics

Antibiotics – the end of an era?

Antibiotics have potentially saved more lives than any other human invention. During the 1940s-1970s, scientists discovered hundreds of new antibiotics, mainly from natural sources, with the best of these developed into drugs able to cure life-threatening infections. Much of this discovery was collaborative.  Academic and industrial researchers worked together to help save lives. Unfortunately, bacteria have adapted so much that many antibiotics are no longer effective at killing them.

superbugs vs antibiotics

Illustration: mmmbitesizescience.com

The microorganisms have evolved a range of ways to avoid their effects, and our ability to discover new antibiotics has not kept up with the bacteria’s ability to become resistant to existing therapies. We now have some infections which cannot be treated by any antibiotic, with patients dying. The scary reality is that these extremely drug resistant bacteria are becoming increasingly common, can readily share their resistance genes with other bacteria, and are being carried around the world by international travelers.

The traditional source of new antibiotics, the large pharmaceutical companies, have largely abandoned this area of research because it is hard to justify economically – they can sell a new anticancer therapy that prolongs a life for nearly $US100,000 per year, but are unable to charge little more than $US5000 for a 2 week course of antibiotics that can save a life.

We need new ways to discover new antibiotics. Antibiotics are different from many other types of drugs, and a lot of the rules developed over the last 20 years for drug discovery projects that focus on ‘drug-like’ properties mean that potential antibiotics might be discarded before they are even tested. The Community for Open Antimicrobial Drug Discovery (CO-ADD) is our attempt to develop a collaborative pipeline of new antibiotic candidates by mining the diverse chemical space of synthetic chemists around the world. Chemists make new molecules for all sorts of reasons, and many of these molecules have unusual structures. However, once made many compounds are either thrown away or just get stored on shelves and in fridges in the backs of labs, and are certainly never tested for antimicrobial activity.

With funding from the Wellcome Trust and support from the University of Queensland, CO-ADD is offering free testing to see if compounds can kill any one of five key pathogenic bacteria or two fungi. Importantly, whoever submits the compound keeps all the rights to publish or patent, and develop any promising compounds. CO-ADD will use the screening data to generate a publically accessible database to allow other scientists to see what types of molecules have antimicrobial activity and, just as importantly, what types don’t.

CO-ADD has had a great reception from the scientific community, with over 80 participating groups from 26 countries sending nearly 20,000 compounds in our first 8 months, with over 300,000 additional compounds promised. We’re currently running a ‘Thinkable’ competition  to award novel ideals for submissions. It’s still too early to see whether we’ll discover the next antibiotic, but we’ve identified nearly 500 compounds with promising activity.

About the author: Dr. Mark Blaskovich is the Program Coordinator for Hit Validation & Chemistry for the Community for Open Antimicrobial Drug Discovery (CO-ADD, see www.co-add.org). He’s also a Senior Research Officer at the Institute for Molecular Bioscience at The University of Queensland in Australia.

Major Breakthrough: First New Antibiotic Discovered in 30 years

It’s a game changer – scientists have discovered a new class of antibiotics which can kill an array of germs by blocking their capacity to build their cell walls, making it extremely difficult for bacteria to evolve resistance. It’s the first such discovery in the past three decades, and comes as a much needed breath of air in the fight against superbugs.

IChip device allows ‘unculturable’ bacteria to be studied for their ability to produce antibiotics. Image credits: Slava Epstein

The antibiotic is called teixobactin and was uncovered by screening 10,000 bacterial strains from soil. Teixobactin has been tested on animals, but it’s still yet to be tested on humans. The results were described in Nature.

New antibiotics, new prospects

“Teixobactin kills exceptionally well. It has the ability to rapidly clear infections,” said research leader Kim Lewis, director of the Antimicrobial Discovery Center at Northeastern University in Boston, US.

The discovery of this antibiotic is exciting from many reasons – first of all, it’s been quite a while since a new class of antibiotics has been developed. Second of all, the way in which teixobactin kills germs is unique and shows great promise; recently, super-strong drug resistant bacteria have caused increased concern in the health community, with no clear solution in sight – this could be a valuable weapon. Also, the way in which they discovered the antibiotic shows great potential. The device has the potential to reveal further undiscovered antibiotics: it enables ‘unculturable’ microbes to thrive in the lab, and so makes it easier to discover bacteria that naturally produce compounds deadly to other pathogens.

“The technology is very cool,” says Gerard Wright, a biochemist at McMaster University in Hamilton, Canada, who was not involved with the study. “Nobody knew if these bacteria produced anything useful.

A Major Breakthrough

A scanning electron micrograph of methicillin-resistant Staphylococcus aureus. Teixobactin kills a wide range of antibiotic-resistant bacteria, including MRSA. Photograph: Mediscan/Corbis

When you look at things in a broader context, the discovery method is even more exciting than the finding itself. A new antibiotic can only go so far, but a new way of finding antibiotics… now that’s a story! Most antibiotics we use today were discovered by scientists in the earlier part of the 20th century, and there’s been no new discovery for almost 3 decades. The antibiotics we know so far are:

1928 – Penicillin
1932 – Sulfonamides
1943 – Streptomycin
1946 – Chloramphenicol
1948 – Cephalosporins
1952 – Erythromycin and Isoniazid
1957 – Vancomycin
1961 – Trimethoprim
1976 – Carbapenems
1979 – Monobactams
1987 – Lipopepitides

As researchers combed through more and more samples, it became harder and harder to find new things; here’s how this team did it. First of all, they understood that the bacteria they were trying to grow simply don’t grow in a lab. Like most organisms, bacteria also take cues from their outside environment – if they don’t receive natural environmental cues, they simply don’t divide; so researchers had to take the bacteria in a different environment.

They suspended them in a lump of agarose (a sugar polymer) and then surrounded the polymer with a semi-permeable membrane which would not let cells through, but would let small molecules through. Then, they transplanted the entire system back into the soiland only then were they able to grow and mutate the bacteria in the lab.

“What most excites me is the tantalising prospect that this discovery is just the tip of the iceberg,” said Mark Woolhouse, professor of infectious disease epidemiology at the University of Edinburgh. “It may be that we will find more, perhaps many more, antibiotics using these latest techniques.”

It it also proves efficient in humans, then we’ll be likely seeing clinical trials in just a couple of years.

Journal Reference: Losee L. et al. A new antibiotic kills pathogens without detectable resistance. Nature (2015) doi:10.1038/nature14098

 

The beginning of the end for antibacterial soaps?

There is very little evidence that anti-bacterial ingredients used in common soaps actually do anything in the long run to fight bacteria – compared to regular soaps. There is however, lots of evidence that they are breeding a new generation of “superbugs” – pathogens which develop resistance to drugs. Basically, reckless use of antibacterial substances and antibiotics is “training” pathogens, which become more and more dangerous. But that might change in the near future.

Triclosan is a potent antibacterial agent able to kill most types of bacteria, both healthy and disease-causing ones. It is commonly used in hospitals, where it likely saved millions of lives from infection. However, it is also used in smaller concentrations for numerous household cleaning products, including antibacterial soaps an pesticides. When bacteria are exposed to low doses of Triclosan (as with any other antibacterial substance), they will use as much energy as possible to protect themselves from the threat; if the dose is low enough, they can succeed – and you end up with a much more resilient “breed” of bacteria. What doesn’t kill them makes them stronger.

Recently, the US Food and Drug Administration (FDA) and the US Environmental Protection Agency (EPA) co-announced they were taking a closer look at how Triclosan is used, in an attempt to limit its use in households and pesticides. There is, as I said, little to no evidence that Triclosan actually has a better effect than its conventional alternatives. The exception here are toothpastes – which have proven to be more effective against gingivitis.

The state of Minnesota has already placed a ban on the substance which will come into effect in 2017, and Johnson & Johnson, Procter & Gamble and Avon have committed to phasing Triclosan out of all their products by 2015. It seems that finally, authorities have started to acknowledge the seriousness of the drug-resistant microbes situation. However, this is just a substance, and it has several other alternatives – but it’s a start.

But we all have to play our part. Avoid reckless usage of antibiotics and antibacterial cleaning products, and stick to regular soap – which is extremely effective as it is.

A recipe for disaster: antimicrobial resistance may lead to dystopian scenarios

AMRfrontpage2A world where even minor infections can kill you, where almost no antibiotics are viable, with superbugs and drug-resistant strains – it’s not a horror movie scenario, but something which may very well happen in the upcoming decades, according to a new report by the World Health Organization (WHO).

We’ve written about the threats of antibiotic resistance before, and how superbugs are becoming more and more prevalent in recent years, but things are really starting to get out of hand. According to the WHO, a post-antibiotic era – in which common infections and minor injuries can kill – is a very possible future.

Antimicrobial resistance (AMR) has developed to threaten the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. The magnitude of the issue is hard to estimate, but the fact is, pathogens seem to develop AMR faster than medicine can develop new strains of antibiotics, so it seems somewhat unavoidable to reach a tipping point one day; that’s what the WHO report concludes as well.

However, the length and magnitude of the study is impressive. The WHO collaborated with member states and other partners, for the first time providing an accurate global picture on the magnitude of AMR and the current state of surveillance globally. The results are worrying. For example, resistance to the treatment of last resort for life-threatening infections caused by a common intestinal bacteria, Klebsiella pneumoniae–carbapenem antibiotics–has spread to all regions of the world. K. pneumoniae is a major cause of hospital-acquired infections such as pneumonia, bloodstream infections, infections in newborns and intensive-care unit patients – and this is not an isolated case.

Resistance to one of the most common treatments to E. coli–fluoroquinolones, which causes urinary tract infections, is also very widespread.

So we’re dealing with a huge problem here, but the good news is that all of us could contribute to solving it. Here are the basic things you can do:

 

  • using antibiotics only when prescribed by a doctor;
  • completing the full prescription, even if they feel better;
  • never sharing antibiotics with others or using leftover prescriptions.

Indeed, a big part of this problem was caused by people who took unnecessary antibiotics and/or didn’t complete the full prescription. Remember, taking antibiotics is a responsibility, first of all to yourself, but to everybody else as well!

Healthworkers can also play their part, which includes:

 

  • enhancing infection prevention and control;
  • only prescribing and dispensing antibiotics when they are truly needed;
  • prescribing and dispensing the right antibiotic(s) to treat the illness.

It’s high time we start understanding the magnitude of this issue, and start tackling it!

Read the full report, as well as other information here.

 

 

Single protein plays key role in almost all lung diseases

From the common cold to pneumonia and potentially life threatening lung diseases: a single protein was found to play a key role. Now, an international team of researchers has finally zeroed in it.

Picture via Dan Meyers | University Communications

The key protein is called MUC5B – it is one of the two proteins found in the mucus that normally and helpfully coats airway surfaces in the nose and lung. Both of them are sugar-rich, and both of them have a similar molecular structure. The other one is MUA5C.

“We knew these two proteins are associated with diseases in which the body produces too much mucus, such as cystic fibrosis, asthma, pulmonary fibrosis and COPD,” said researcher Chris Evans, PhD, an associate professor in the University of Colorado School of Medicine. “We also knew that many patients with asthma or COPD have as much as 95 percent less MUC5B in their lungs than healthy individuals, so we wanted to see if one of these is the bad player in chronic lung diseases.”

The researchers compared mice with both these proteins with mice who lacked one or the other. The ones that lacked MUC5AC were fine, but the one without MUC5B constantly got sick. Their immune systems were also much more vulnerable, especially to the MRSA “superbug,” a major source of infections in hospitals and even in day to day situations.

This has very important implications for people with runny noses – what this means is that getting rid of the mucus, as good as that may make you feel, may do more harm than good.

“Getting rid of your mucus may make you more comfortable and may help patients with chronic lung diseases,” Evans said. “But if you block it too effectively, this actually could be harmful in the long run. If a treatment gets rid of MUC5B, it may make people more vulnerable to additional infections.”

Interestingly enough, the MUC5B protein is encoded in a part of the human genome which shows great variability. For example, every 1 in 5 people have a mutation that causes them to produce 30 times more protein than usual. It’s still not clear what the effects of too much MUC5B are.

“Knowing the key role of MUC5B allows us now to focus on how the protein works and, we hope, to find ways to help patients with these diseases,” Evans said.

Via University of Colorado Denver.

Low level of antibiotics cause drug resistance in ‘superbugs’

For years and years (good) doctors have warned about the dangers of taking antibiotics too lightly, which generally causes ‘bugs’ to be more resistant. More recently, a study conducted by researchers from Boston University showed that microbes are a lot like us: what doesn’t kill them makes them stronger, and this could have extreme consequences. Here’s what it’s about.

You’re sick, you go to the doctor, he gives you a prescription. You start taking it, after a couple of days feel all better, and stop taking it. The result is likely a strain of bacteria (or virus) that will be resistant to a whole number of drugs. The same thing could happen if you’re sick and instead of going to the doctor just take those pills you’ve got, and avoid going to the doctor alltogether.

superbugBasically, when administered in lethal levels, antibiotics trigger a fatal chain reaction within the bacteria that shreds the cell’s DNA. However, when the level is less than the lethal one, the results are not only the survival of the bacteria and the further resistance to this drug, but also to a whole series of other ones too.

“In effect, what doesn’t kill them makes them stronger,” said Collins, who is also a Howard Hughes Medical Institute investigator. “These findings drive home the need for tighter regulations on the use of antibiotics, especially in agriculture; for doctors to be more disciplined in their prescription of antibiotics; and for patients to be more disciplined in following their prescriptions.”

“We know free radicals damage DNA, and when that happens, DNA repair systems get called into play that are known to introduce mistakes, or mutations,” said Collins. “We arrived at the hypothesis that sub-lethal levels of antibiotics could bump up the mutation rate via the production of free radicals, and lead to the dramatic emergence of multi-drug resistance. The sub-lethal levels dramatically drove up the mutation levels, and produced a wide array of mutations,” Collins observed. “Because you’re not killing with the antibiotics, you’re allowing many different types of mutants to survive. We discovered that in this zoo of mutants, you can actually have a mutant that could be killed by the antibiotic that produced the mutation but, as a result of its mutation, be resistant to other antibiotics.”