Exciting new discovery pipeline delivers MRSA active antibiotics
Researchers have found new antibiotics that also restore beta-lactam activity in resistant strains.
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.
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.
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