January 7, 2015

expert reaction to identification of a new antibiotic, effective in treating mice

A study published in the journal Nature has reported the discovery of a new antibiotic from a screen of soil bacteria, and its use in mice to treat MRSA and S. pneumoniae infections. They state an inability to grow bacterial mutants which were resistant to the antibiotic, suggesting that it may be useful for developing treatments for use in humans.

Prof. Laura Piddock, Professor of Microbiology, University of Birmingham, said:

“The screening tool developed by these researchers could be a ‘game changer’ for discovering new antibiotics as it allows compounds to be isolated from soil producing micro-organisms that do not grow under normal laboratory conditions.

“If teixobactin can be formulated into a new drug for patients, it could be used to treat infections such as tuberculosis or those caused by MRSA.

“Teixobactin has no activity against Gram-negative bacteria such as E. coli. However, the iChip tool developed by Kim Lewis and colleagues can now be applied to find natural products with activity against these microorganisms.”

Prof. Mark Woolhouse, Professor of Infectious Disease Epidemiology, University of Edinburgh, said:

“Any report of a new antibiotic is auspicious, but what most excites me about the paper by Lewis et al. is the tantalising prospect that this discovery is just the tip of the iceberg. Most antibiotics are natural products derived from microbes in the soil. The ones we have discovered so far come from a tiny subset of the rich diversity of microbes that live there. Lewis et al. have found a way to look for antibiotics in other kinds of microbe, part of the so-called microbial “dark matter” that is very difficult to study. Others have done the same thing using different approaches. It may be that we will find more, perhaps many more, antibiotics using these latest techniques. We should certainly be trying – the antibiotic pipeline has been drying up for many years now; we need to open it up again, and develop alternatives to antibiotics at the same time, if we are to avert a public health disaster.”

Dr Angelika Gründling, Reader in Molecular Microbiology, Imperial College London, said:

“Antimicrobial resistance is a widespread problem that is slowly undermining our ability to treat common bacterial infections. The study by Ling et al., which describes the discovery of a new antibiotic that kills a large range of bacteria, raises our hopes that new antibiotics can be brought to the clinics in the not too distant future. The authors used an old strategy, looking for antimicrobials naturally produced by bacteria, but now with a new and important twist – in a new group of bacteria, which in the past were considered unculturable. The authors developed a method to propagate many of these ‘unculturable’ bacteria, which allowed them to tap them as a source of new antimicrobials. The great hope is now that many more new antibiotics can be uncovered in a similar manner. This study is also a great testimony for the technological advances that have been made in recent years and the speed with which one can now progress from the discovery of a new compound, to the identification of it chemical structure, its producer down to the genes coding for the enzymes required for its production.

“But before getting too carried away, it’s important to bear in mind that the new antibiotic only works against certain types of bacteria – such as MRSA and Streptococcus, and not on other multi-drug resistant pathogens such as E. coli, Klebsiella and Pseudomonas, which are all major causes of infection in humans. And of course the new antibiotic described in the paper has yet to be tested in humans. It is possible that it might not be as effective as hoped and there could be unforeseen side-effects that might limit its use.”

Prof. Nigel Brown, President, Society for General Microbiology, said:

“As a microbiologist I am delighted to learn of this new antibiotic, which represents a much-needed new class of drug, especially as there has yet to be indications of any resistance developing. We desperately need new antibiotics to tackle bacterial infections – this is a very promising development.”

Prof. Timothy Walsh, Institute of Infection and Immunity, Cardiff University, said:

“This new antibiotic, Teixobactin, is directed at Gram-positive bacteria like MRSA. The exciting development in mice is more directed towards the technology used to recover and grow bacteria which hitherto was not possible.

“The article describes a multichannel device, the iChip10, which was used to simultaneously isolate and grow uncultured bacteria and by doing so use these ‘friendly bacteria’ as a unique source of antibiotics that can inhibit or kill pathogens in mice that also affect humans.

“Whilst anti-Gram-positive antibiotics are useful, the global clinical community is desperate for new, and even novel antibiotics against multi-drug resistant Gram-negative bacteria. However, further exploitation of this technology can, and potentially should, meet this clinical challenge.”

Prof. Chris Butler, Director of the Institute of Primary Care and Public Health, Cardiff University, said:

“Discoveries of truly new antibiotic classes are indeed rare and to be warmly welcomed, given the inexorable rise in gram-negative bacterial resistance.

“While exciting, this is very early phase research and we have no idea if this agent will be safe or effective in humans.

“As the authors rightly point out, resistance usually does emerge to new antibiotics, so if future trials show that this antibiotic is suitable for widespread use in humans, we have to treat it as a precious shared resource.”

Dr Bob Lauder, Associate Dean in the Faculty of Health and Medicine, Lancaster University, said:

“The search for new antibiotics is an enormous challenge, and this work reports a major development in this arena. The importance of this arena is seen in the fact that the Longitude Prize 2014 chose antibiotic resistance as the topic for the prize from a wide range of really major social issues such as dementia and the provision of safe drinking water and food.

“Antibiotics made many conditions which were normally fatal, survivable, and so they have had an enormous impact on all of our lives. However, the widely recognised danger of antibiotic resistance, when bacteria develop resistance to an antibiotic rendering it much less useful, could undermine the progress in healthcare in this area made over the last 70 years.

“The costs of discovering, developing and testing a new antibiotic are huge and the financial risks are large as the antibiotic may have a limited lifespan if bacterial resistance develops. In fact few new antibiotics have been identified in the last 30 years and so this thorough study, is a welcome development in a field looking for new advances.

“The antibiotic identified is a bacterial product; produced by one soil bacteria to stop the growth of others. However, rather than grow these using conventional microbiological approaches, the approach taken by this group was to explore antibiotic production in the soil. This allowed them to access the products from bacteria which cannot be cultured in a lab. In fact it is likely than the vast majority of bacteria in soil cannot easily be cultured in the lab, and so this is likely to be an approach which is more widely used in the future to access novel antibiotics.

“The authors have conducted a detailed and thorough study which has reported the structure of this new antibiotic. Although this is a complex molecule it has a structure which is very likely to be suitable for synthesis, and hence production at a cost and scale which would be appropriate for a therapeutic material.

“The report is very exciting but more work needs to be done before this new antibiotic can be used. While the initial toxicity studies reported suggest that it will likely be safe to use, that work needs to be developed. In addition more detailed studies will be needed to understand dosage, how much and how often should it be taken. The data suggest that it may be cleared from human plasma quite quickly.

“This new antibiotic appears to work in an interesting way, attacking key parts of the bacterial coat. While that may make it less likely that antibiotic resistance develops, that’s not a certainty and we’ll all need to use this new compound, and any others developed carefully, otherwise we risk wasting the potential this antibiotic has.”

Prof. Roger Pickup, Associate Dean for Research, Lancaster University, said:

“This is a very exciting development.  In the microbial world the uncultured majority, which constitutes >99.9% of all bacteria, are rarely exploited for their products.  Tapping into this vast resource by culture has been unfunded by government and industry, perhaps as it not considered exciting science in comparison to the characterisation of the microbial world by methods such as the next generation sequencing. Coupled with the reluctance of the pharmaceutical industry to fund the discovery of new antibiotics, the identification of this new antibiotic in this often unexplored sphere of microbiology is very exciting. This may lead to the discovery of more unique antibiotics that can come on line and replace, or work in tandem, with current therapies that fight infection, particularly those caused by bacteria currently resistant to the spectrum of antibiotics available to us at present.

“These ‘magic bullets’ have been discovered before only to have their effectiveness whittled away by the emergence of  bacteria resistant to those antibiotics. Although the prediction that developing bacterial resistance to Teixobactin will be more difficult due to its mode of action, precaution is a key principle here. Bacteria are tenacious in their ability to rapidly evolve and become resistant to antibiotics; lessons have been learnt from the current antibiotic crisis and these must implemented if Teixobactin is to be an effective readily available drug for fighting infection. These lessons include educating the public and medical professionals to prevent indiscriminate use of prescriptions (this drug will not fight cold and flu [viral diseases]), controlling its use in farming and animal production and using it as a second line defence if current antibiotics fail. Hopefully the pharmaceutical industry will take note of this discovery and direct funds to explore and exploit the bacteria that, at present, remain uncultured.”

Prof. Neil Woodford, Head of Public Health England’s Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, said:

“Public Health England welcomes the development of new therapies that can be used to treat bacterial infections successfully. The rise in antibiotic resistance is a threat to modern healthcare as we know it so this discovery could potentially help to bridge the ever increasing gap between infections and the medicines we have available to treat them.

“Although this is a step forwards, this new discovery would not be suitable for treating infections caused by E.coli, Klebsiella or other Gram-negative bacteria. These are the focus of many concerns about antibiotic resistance and finding a new potential treatment for these would be a major breakthrough.

“Taking any potential antibacterial compound from discovery to successful licensing is a long, costly and difficult process.  However it is one that needs to be encouraged while we tackle other elements that contribute to the development of antibiotic resistance and seek to preserve the antibiotics we do have.”

Dr Richard Seabrook, Head of Business Development at the Wellcome Trust, (Richard Seabrook works in innovation and technology transfer at the Wellcome Trust, including managing funding for drug seeding, quite a few of which are antimicrobials) said:

“Although still in the early stages of research, the discovery of a potential new class of antibiotics is good news: the development of new antibiotics has stalled in recent decades, while resistance to existing drugs becomes an ever more serious threat to human health. Screening previously unculturable soil bacteria is a new twist in the search for novel compounds that might have antibiotic potential and it is encouraging to see this approach yielding results. However, we will not know whether teixobactin will be effective in humans until this research is taken from animal testing in the lab to clinical trials.”

‘A new antibiotic kills pathogens without detectable resistance’ by Losee L. Ling et al. published in Nature on Wednesday 7 January 2015. 

Declared interests

None declared