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Marine Mammal Microbiota Yields Novel Antibiotic with Potent Activity Against Clostridium difficile
journal contribution
posted on 2017-10-18, 14:23 authored by Jessica L. Ochoa, Laura M. Sanchez, Byoung-Mo Koo, Jennifer S. Doherty, Manohary Rajendram, Kerwyn Casey Huang, Carol A. Gross, Roger G. LiningtonThe
recent explosion of research on the microbiota has highlighted the
important interplay between commensal microorganisms and the health
of their cognate hosts. Metabolites isolated from commensal bacteria
have been demonstrated to possess a range of antimicrobial activities,
and it is widely believed that some of these metabolites modulate
host behavior, affecting predisposition to disease and pathogen invasion.
Our access to the local marine mammal stranding network and previous
successes in mining the fish microbiota poised us to test the hypothesis
that the marine mammal microbiota is a novel source of commensal bacteria-produced
bioactive metabolites. Examination of intestinal contents from five
marine mammals led to the identification of a Micromonospora strain with potent and selective activity against a panel of Gram-positive
pathogens and no discernible human cytotoxicity. Compound isolation
afforded a new complex glycosylated polyketide, phocoenamicin, with
potent activity against the intestinal pathogen Clostridium
difficile, an organism challenging to treat in hospital settings.
Use of our activity-profiling platform, BioMAP, clustered this metabolite
with other known ionophore antibiotics. Fluorescence imaging and flow
cytometry confirmed that phocoenamicin is capable of shifting membrane
potential without damaging membrane integrity. Thus, exploration of
gut microbiota in hosts from diverse environments can serve as a powerful
strategy for the discovery of novel antibiotics against human pathogens.
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commensal microorganismsMicromonospora strainnovel antibioticscommensal bacteria-produced bioactive metabolitesglycosylated polyketideflow cytometryactivity-profiling platformcommensal bacteriahospital settingsfish microbiotapathogen ClostridiumGram-positive pathogensgut microbiotaionophore antibioticsCompound isolationphocoenamicinPotent Activitymarine mammalsmembrane integritymarine mammalFluorescence imaginghost behaviorantimicrobial activitiesnovel sourcepathogen invasionmarine Mammal Microbiota Yields Novel Antibioticmarine mammal microbiota
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