New 'game-changing' antibiotic discovered

Behind the Headlines

Thursday January 8 2015

Teixobactin works by destroying the cell walls of bacteria

The new antibiotic proved effective against MRSA

“New class of antibiotic could turn the tables,” on antibiotic resistance, The Guardian reports and is just one of many headlines proclaiming the discovery of a “super-antibiotic”. For once, such enthusiastic headlines might be largely justified.

The study in the spotlight shows the discovery of a new antibiotic, teixobactin, and is exciting for two main reasons.

Firstly, teixobactin proved effective against certain types of drug-resistant bacteria such as MRSA and tuberculosis (TB) in mice models. The way it works, by attacking cell walls rather than proteins, also suggested that bacteria would have a hard time evolving around its effects to develop resistance. This is the first potentially new antibiotic in over 20 years.

Secondly, the mechanism of discovery is potentially revolutionary. The research team used a device known as an iChip to make bacteria in soil “lab-ready” for use. Previously, only 1% of the organisms in soil could be grown and studied in the laboratory. This leaves 99% of bacteria as an untapped source of new antibiotics useful to people. Unlocking this natural reservoir of antibiotic production could potentially lead to the discovery of many more antibiotics in the future.

We now need to wait for tests on humans to make sure that teixobactin works and is safe. Also, teixobactin only appears to be effective against a subset of bacteria (Gram-positive bacteria), so is not a cure-all for Gram-negative bacterial infections, which include E.coli.

This is genuinely exciting news, but only time will tell whether this is a historical moment of similar magnitude to that of Alexander Fleming’s original discovery of penicillin in 1928.

 

"Antimicrobial resistance poses a catastrophic threat. If we don’t act now, any one of us could go into hospital in 20 years for minor surgery and die because of an ordinary infection that can’t be treated by antibiotics. And routine operations like hip replacements or organ transplants could be deadly because of the risk of infection”.

Professor Dame Sally Davies, Chief Medical Officer

 

Where did the story come from?

The study was carried out by researchers from the US, Germany and the UK, and was funded by the US National Institutes of Health, the Charles A King Trust, German Research Foundation and the German Centre for Infection Research.

Many of the authors declare financial conflicts of interest, as they are employees and consultants of NovoBiotic Pharmaceuticals, a biotech firm with an interest in creating new drugs.

The study was published in the peer-reviewed science journal Nature.

The study attracted widespread attention from both the UK and international media. Generally, the media reported the story accurately, with many highlighting that while the study was promising, no human tests had yet taken place.

 

What kind of research was this?

This was a laboratory and mice study looking for new antibiotics.

Antibiotics – chemicals that kill bacteria – were first found in the early 20th century. This led to an explosion of antibiotic discovery that revolutionised medicine, and provided cures for previously incurable diseases. It also led to a marked decrease in complications arising from infection during surgical procedures we now regard as routine and safe, such as caesarean sections.

However, there have been no new antibiotic discoveries for decades. Existing antibiotics are becoming less effective because some bacteria are not killed by them and these bacteria can spread over time; these are so-called "drug-resistant bacteria".

Most people are aware of the "superbugs", such as MRSA and C-difficile, which are a leading cause of hospital-based infections. There are other candidates out there, such as extensively drug-resistant TB, which can take up to two years to treat. Therefore, the problem of drug-resistant bacteria is serious and growing, and could pose one of the greatest threats to public health in the 21st century.

This research sought to identify new bacteria from soil, which is heaving with micro-organisms harbouring naturally occurring antibiotics. Amazingly, the researchers tells us, only 1% of the organisms in soil can be grown and studied in the laboratory. This means the remaining 99% are potentially an untapped source of new antibiotics.

The team sought to devise a new way of growing and studying some of the soil micro-organisms, to screen them for any that display antibiotic properties and could be turned into new drugs.

 

What did the research involve?

The team designed and tested a number of methods to grow (culture) previously un-growable (unculturable) micro-organisms from soil.

This including making a device (iChip) that could be immersed in soil to “trick” the organisms into growing, but still allowed the team to isolate the micro-organisms for further study. This was used alongside a range of chemical growth factors to encourage and maintain growth.

When successful, they screened the newly cultured organisms for any signs that they were producing antibiotics. A number of new chemicals that looked promising were found and then tested in mice, including mice infected with methicillin-resistant Staphylococcus aureus (MRSA).

 

What were the basic results?

The results revealed a number of striking new discoveries:

  • Researchers could successfully grow a range of new organisms from the soil, which had never been done before.
  • Some of these newly grown organisms naturally produced antibiotics.
  • One such antibiotic, named teixobactin, was particularly promising and was subsequently studied intensely in the laboratory and in mice.
  • Tests in mice revealed teixobactin was effective against Gram-positive bacteria including MRSA and the bacteria that cause TB. However, it was not effective against Gram-negative bacteria such as E.coli, which have an extra layer of cell wall protection.
  • Teixobactin inhibited cell wall synthesis via a mechanism that bacteria are unlikely to develop resistance to, as it is so fundamental to their normal survival.
  • Backing this up, when teixobactin was used against bacteria Staphylococcus aureus or Mycobacterium tuberculosis no drug-resistant bacteria were found or developed. This is unusual, as most tests reveal some naturally occurring resistance over time.

 

How did the researchers interpret the results?

The research team simply concluded that: “The properties of this compound [teixobactin] suggest a path towards developing antibiotics that are likely to avoid development of resistance.”

 

Conclusion

This study shows the discovery mechanism of teixobactin and is exciting for two reasons. Teixobactin by itself shows effectiveness against MRSA and TB in mice models and has properties indicating that drug resistance may be unlikely to develop. This is encouraging for the potential future development of it for human diseases caused by Gram-positive bacteria.

Also, the mechanism of discovery shows great promise. The research team devised a completely new way of growing micro-organisms from soil that could not previously be grown. These micro-organisms, 99% of which are unknown to science, have the potential to produce natural antibiotics. Therefore, this discovery opens up the possibility that many more antibiotics can be found in the future. This is encouraging as there has been a lack of new antibiotic discoveries since the 1980s, while at the same time, the problem of drug-resistant bacteria has been growing.

While this discovery is undoubtedly good news, there are a number of moderating factors to bear in mind:

  • We don’t know what proportion of the 99% of currently ungrowable bacteria this new method will help to unleash, and what proportion of them might yield useful antibiotics.
  • Teixobactin has so far only been trialled in the lab and in mice. We need to await tests in humans before we can be sure it works and is safe.
  • Teixobactin looks effective against a subset of bacteria only (Gram-positive bacteria) so is not a cure-all for bacterial diseases.

With these limitations in mind, for once a study matches up to the media hype, as it discovered a promising new antibiotic candidate (teixobactin) and shows us a method that has the potential to lead to many more.

It is early days, but we could potentially be heading into a future where antibiotic-resistance is a thing of the past.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Analysis by Bazian

Edited by NHS Choices

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