Exciting new discovery pipeline delivers MRSA active antibiotics

Researchers have found new antibiotics that also restore beta-lactam activity in resistant strains.

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Oct 20, 2016
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In the summer, a new, nonribosomally synthesised peptide antibiotic was discovered from a Staphylococcal species in the human nose. Researchers cultured S. lugdunensis and isolated the active compound lugdunin, declaring the the human microbiome could be a gold mine of antibiotics of the future.

Researchers in the USA have now used the human microbiome to discover a brand new, nonribosomally synthesised peptide antibiotic with potent activity against MRSA.

But there is a twist, the American team lead by Sean Brady did not culture any bacteria in their pursuit of antibiotics. Instead, they analysed human microbiome sequences looking for nonribosomally synthesised peptides and identified several target that they then chemically synthesised.

They found that one of the peptides which they named "humimycin A" had potent antimicrobial activity against many staphylococcal isolates. They also discovered that humimycin A was able to restore beta-lactam activity in MRSA strains.

For the full text of the paper, go here.


Abstract

Here we present a natural product discovery approach, whereby structures are bioinformatically predicted from primary sequence and produced by chemical synthesis (synthetic-bioinformatic natural products, syn-BNPs), circumventing the need for bacterial culture and gene expression. When we applied the approach to nonribosomal peptide synthetase gene clusters from human-associated bacteria, we identified the humimycins. These antibiotics inhibit lipid II flippase and potentiate β-lactam activity against methicillin-resistant Staphylococcus aureus in mice, potentially providing a new treatment regimen.

Reference

Discovery of MRSA active antibiotics using primary sequence from the human microbiome

John Chu, Xavier Vila-Farres, Daigo Inoyama, Melinda Ternei,Louis J Cohen, Emma A Gordon, Boojala Vijay B Reddy, Zachary Charlop-Powers, Henry A Zebroski, Ricardo Gallardo-Macias, Mark Jaskowski, Shruthi Satish, Steven Park, David S Perlin, Joel S Freundlich & Sean F Brady

Nature Chemical Biology (2016)doi:10.1038/nchembio.2207

Go to the profile of Ben Libberton

Ben Libberton

Communications Officer, MAX IV Laboratory

I'm a Communications Officer at MAX IV Laboratory in Lund, Sweden, formally a Postdoc in the biofilm field. I'm interested in how bacteria cause disease and look to technology to produce novel tools to study and ultimately prevent infection. Part of my current role is to find ways to use synchrotron radiation to study microorganisms.

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