A superdrug to fight the superbug? A resistance-proof antibiotic and the tool that discovered it.

The iChip.

Image adapted from reference (3).

Imagine a world without antibiotics. Imagine a world where an ear infection is a death sentence. This was the case less than one hundred years ago, and most of us cannot even imagine it. One of the most revolutionary discoveries in medical history was that of the antibiotic, but with few new antibiotics and an ever-increasing number of drug-resistant bacteria, many fear we may return to this pre-antibiotic age. However, with the promising results of a recent technology, a new era of developing unique antibiotics to which resistance is unlikely to develop may be upon us.

If it weren’t for antibiotics, diseases like pneumonia, tuberculosis, and gangrene would still be a constant threat. Now, at least in the Western world, human life is no longer so fragile. However, few new antibiotics have been developed since the 1960s. In the 1940s, Selman Waksman took advantage of the millions of years bacteria have spent fighting each other and developed a successful method to systematically check bacterial strains for antibiotics, but soon new compounds were scarcely found. This would be less problematic if the rapid life cycle of bacteria didn’t allow it to develop resistance against existing drugs. ‘Superbugs’ like methicilin-resistant Staphylococcus aureus (MRSA) and other hospital-borne pathogens are becoming a real threat. The overuse and misuse of antibiotics, which increase the likelihood of drug-resistant bacteria, is getting worse. Almost more worrying, low profit margins make antibiotic development unappealing to pharmaceutical companies.

Lifting the spirits of even the most pessimistic is the recent discovery of the antibiotic ‘teixobactin’ found with the help of the ‘iChip’. In this project lead by Kim Lewis at Northeastern University in Boston, the new antibiotic eliminates Staphylococcus aureus infections both on a Petri dish and in mice, without any resistance development. Why is this new drug being discovered now? Lewis’s team used a simple but innovative technology, the iChip, to culture types of bacteria not previously culturable. Only 1% of soil bacteria can survive in the lab environment of the Waksman method. With the iChip, this number rises to 50%. Cells are harvested from the soil and separated into the tiny compartments of the iChip. The device is then returned to the soil, and nutrients pass through semi-permeable membranes while the different bacteria remain separated.

Screening this new series of bacterial strains to see which would fight off Staphylococcus aureus, the team found Eleftheria terrae. Screening all the chemicals produced by the new bacteria, they found teixobactin. When in further tests, teixobactin neither resulted in resistance nor toxicity in mammalian cells, the team thought their finding was too good to be true. However, when they found it likely bound two lipids in the membrane of S. aureus, not present in mammalian cells, these properties began to make sense. When teixobactin is bound to it one of the lipids prevents the creation of new membrane while the other induces the destruction of it.

Because teixobactin binds the lipid directly, resistance development would happen differently than for other antibiotics. Penicillin, for example, gets its antibiotic properties by binding an enzyme involved in building the membrane. Small changes in this large enzyme can evolve to remove penicillin binding without changing the activity of the enzyme. Any change in these small lipids that would prevent teixobactin from binding is likely to also have wild functional consequences for the bacteria itself. This is probably why resistance to teixobactin has not been seen so far, not to mention that teixobactin binds two lipids simultaneously.

While all of this is promising, it is important to note that this is still early stages. Further tests of resistance and toxicity in humans will be necessary. While the initial data shows teixobactin is more effective at clearing MRSA than the current standard vancomycin, teixobactin is not likely to be in hospitals for at least another few years. The commercialization and FDA approval process can be long, and so far no human studies have even been mentioned. Additionally, teixobactin is only effective against bacteria with these specific lipids, called gram-positive bacteria, and there are many infections that are caused by gram-negative bacteria, toward which teixobactin is not effective. In this light, the most promising aspect of this study is the proof of concept of the iChip: even if teixobactin isn’t our answer, the iChip can be used to help screen the other 49% of bacteria that have previously been inaccessible to laboratory techniques, and hopefully this world without antibiotics will remain one we can’t even imagine.

References

(1) Original Article: http://www.nature.com/nature/journal/v517/n7535/full/nature14098.html

(2) Nature News Article: http://www.nature.com/news/promising-antibiotic-discovered-in-microbial-dark-matter-1.16675

(3) iChip: http://aem.asm.org/content/76/8/2445

This post slightly modified from part of an application for the

AAAS Mass Media Science & Engineering Fellows Program.

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