Thursday, 22 January 2015

Antibiotics really matter and need more research funding

Last year, I went down with tonsillitis on New Year’s Eve. The timing sucked a bit but I guess there are no good times for such things to happen. However, I was/am lucky: lucky because I live in an age where antibiotics are available and still work.

As a scientist, I often get frustrated about science funding. Firstly, there’s not enough of it (compared to other endeavours of less benefit to both society and the economy) but secondly, a lot of it goes to the wrong places, namely human diseases such as cancer. Don’t get me wrong: I’d love to see cancer cured. It’s just that there are bigger fish to fry, and global crises looming that would make diseases of old age such as cancer and Alzheimer’s a bit of a moot point.

An obvious need of greater funding is climate change, thrown into the spotlight again (as if it were needed) by the confirmation that 2014 was the the warmest year on record. Another is the development of new antibiotics.

Antibiotic resistance is a big problem and one that is currently only getting worse. We are heading for a “post antibiotic world”, which is a really scary thought. Indeed, some scientists have argued that antibiotic resistance is a bigger problem than climate change because we have the technology to combat climate change, we just lack the political will. We do not yet have the technical solution to the impending “antibiotic apocalypse”, hence the real need to throw money at research into solutions.

The annoying thing is that this is not a problem that has snuck up on us. In an editorial from 1997 entitled “Antibiotic Armageddon”, Calvin Kunin from The Ohio State University wrote:

“The advances of the antimicrobial era are being dissipated by the emergence and spread of resistant microorganisms, the inevitable consequence of intense use of antibiotics in humans over the past 50 years. The process is accelerating in the community as well as in hospitals and is a problem worldwide. The attrition of older drugs is sustained by the selective effects of new and more expensive drugs developed to overcome resistance. Novel compounds will no doubt be discovered, but their demise is inevitable. It is just a matter of time until resistant pyogenic organisms join the opportunistic microbes as major threats to humans.”

“[The] long-term outlook for control of antibiotic resistance is bleak. There are simply too many physicians prescribing antibiotics casually and too many people buying antibiotics without a prescription in developing countries. There is only a thin red line of infectious diseases practitioners who have dedicated themselves to rational therapy and control of hospital infections. The issues need to be presented forcefully to the medical community and the public. Third-party payers must get the message that these programs can save lives as well as money.”

Sadly, if these words were written today, I don’t think anyone would argue the point; not much has changed. And that’s without even mentioning the big problems caused by the long-running over-use of antibiotics is agriculture.

Things are not without hope. Earlier this month, a Nature paper by Lin et al. reported the discovery of a novel class of antibiotic from a screen of 10,000 bacterial strains, following the development of novel method to grow hitherto uncultured bacteria:

“Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.”

Personally, I remain skeptical about claims that teixobactin is resistance-proof. It may not be easy but I am sure the bugs will stumble across a way to evade or destroy the toxin and evolve resistance. Nonetheless, the message is clear: there are new antibiotics out there to be found. This one was found in the backyard of one of the researchers! Bacteria have been killing each other for millions, maybe billions, of years and so the global diversity in nature is likely to be massive. We just need the ingenuity and funding to find them.

References

Farrar J & Woolhouse M (2014). Policy: An intergovernmental panel on antimicrobial resistance. Nature 509:555–557

Kunin CM (1997). Antibiotic Armageddon. Clinical Infectious Diseases 25:240–1

Lin LL et al. (2015). A new antibiotic kills pathogens without detectable resistance. Nature doi:10.1038/nature14098

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