Editors' ChoiceMicrobiome

Blow the germs away

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Science Translational Medicine  31 Aug 2016:
Vol. 8, Issue 354, pp. 354ec139
DOI: 10.1126/scitranslmed.aah6074

At a time when we are plagued by the emergence of antibiotic-resistant bacteria, we may not need to look very far to identify new antimicrobial compounds with a low likelihood of resistance. Conventional wisdom has driven us to mine bacteria in soil to identify new antimicrobials, given the high microbial diversity in soil. However, a recent study by Zipperer et al. has identified a new antibiotic produced by commensal bacteria inhabiting the nasal cavity of humans, suggesting that we may have been ignoring a more obvious and much more local source of antimicrobials.

Staphylococcus is an opportunistic pathogen that colonizes various parts of the human body and is found in the nose in about 30% of the human population. Methicillin-resistant Staphylococcus aureus is a common cause of infections and can colonize prosthetic heart valves, causing endocarditis and other systemic effects, if it enters the bloodstream. A preventive approach has been to decolonize susceptible individuals using conventional antibiotics, risking the development of antibiotic resistance. Zipperer et al. took advantage of the ability of commensal microbes in the nose to prevent S. aureus from inhabiting this location, highlighting an alternate strategy for preventing S. aureus colonization. To identify mechanisms by which individuals were resistant to nasal colonization by S. aureus, the authors initially identified staphylococcal species that were more often found in the nose in the absence of S. aureus. Among these isolates, the authors discovered Staphylococcus lugdunensis, which was able to inhibit growth of S. aureus in culture plates. Then using a library of S. lugdunensis mutants, they identified a peptide antibiotic “lugdunin” that was responsible for this inhibition and additionally found that it was also able to inhibit vancomycin-resistant Enterococcus. Lugdunin likely acts on the bacterial cell membrane but the exact mechanism remains to be elucidated. It is encouraging, however, that at least in culture, S. aureus did not develop resistance to this new antibiotic.

Lugdunin is the newest addition to the short list of antimicrobials from the commensal microbiota, which includes antibiotics like lactocillin and bacteroicins like thuricin. The new study highlights a missed opportunity and provides a strategy for identifying new antibiotics—that is, taking advantage of natural exclusion of pathogens by commensal microbes in the human body and identifying new gene clusters encoding antibiotic production within the commensal microbiota. Whereas the efficacy of lugdunin needs to be established in human studies, it provides much-needed optimism in our search for new antimicrobials.

A. Zipperer et al., Human commensals producing a novel antibiotic impair pathogen colonization. Nature 535, 511–516 (2016). [Abstract]

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