Mining soil for new antibiotics

Methicillin-resistant Staph aureus. Photo NIAID

The beginning of 2015 brought (potentially) good news for medicine: the discovery of a new antibiotic - teixobactin - isolated from soil bacteria. This result was published in Nature on January 22. (Unfortunately the whole text is not visible without payment or subscription.) Many newspapers and news outlets covered the story in early January, for instance the Guardian, and the New York Times. Teixobactin is a small peptide that acts as an inhibitor of cell wall synthesis in Gram-positive bacteria, which means it can kill pathogens like drug-resistant Staphylococcus aureus (often referred to as MRSA, or methicillin-resistant S. aureus).

The issue at stake here is, of course, the increasing prevalence of antibiotic-resistant bacteria worldwide, a situation well summarized in an article at Swissinfo.ch. We have thus seen a dramatic increase in resistant strains of, for instance, S. aureus, Escherichia coli and Klebsiella pneumoniae. Who or what is to blame? Most probably the overuse of antibiotics, not only in humans but also in animals. It is frightening to know that some pathogenic strains can survive our entire arsenal of antibiotics, while new potent drugs are extremely hard to find. Some simple solutions have helped mitigate the problem, notably more effective and systematic hand disinfection by hopital personnel, but this will not prevent all cases of infection. New antimicrobials are clearly needed, but where to find them?



Historically, soil bacteria have been our major source of antimicrobial compounds, particularly the genus Streptomyces. The discovery of new antibiotics from soil bacteria, however, has stalled in the past decades. One obvious reason is that we have already collected the low-hanging fruits: that is, compounds that are easy to isolate from bacteria that easily grow in the laboratory. The pool of remaining antimicrobial compounds in nature might be enormous, but the effort to mine it is substantial. This is what makes the paper by Ling and colleagues so interesting: it shows that we can extract useful drugs from soil microorganisms that are not readily cultivable in the laboratory.

Structure of Teixobactin. Source Wikimedia commons.

This feat was achieved by an international team of researchers from Northeastern University in Boston,  the University of Bonn, and the biotech company NovoBiotic Pharmaceuticals. To isolate the soil bacteria, they used a clever device named the iChip (Nichols et al., 2010, and see also this interesting post at Popular Science). This chip, designed by the group of Slava Epstein, consists of 192 microwells isolated between two permeable membranes. Once trapped in a microwell, the bacteria can be cultivated directly in soil (where the bacteria can be in contact with soil nutrients, but cannot escape), as opposed to classic plating techniques on Petri dishes. The screening of ~10,000 individual soil isolates permitted the discovery of a new species - named Eleftheria terrae, and belonging to beta-Proteobacteria -, which produces teixobactin. Needless to say, the iChip could lead to the discovery of many other uncultivable species producing compounds of medical importance. This is a great example of how the quest for new drugs is taking place in natural environments rather than in chemical synthesis lab (see for instance my previous post on mining the deep sea for active compounds).

One downside is that teixobactin is only active against Gram-positive bacteria (Staphylococcus, Bacillus, Clostridium, Mycobacterium, etc.), whereas the most pressing problems are related to Gram-negative species. This notwithstanding, the discovery of teixobactin is a step in the right direction.

References:

• Ling, L. L.,  et al. (2015) A new antibiotic kills pathogens without detectable resistance. Nature 517: pp.455-459.
• Nichols, D., et al. (2010) Use of iChip for high-throughput in situ cultivation of "uncultivable" microbial species. Applied Environmental Microbiology 76(8): pp. 2445-2450.