A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics.

TitleA systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics.
Publication TypeJournal Article
Year of Publication2014
AuthorsDonia, MS, Cimermancic, P, Schulze, CJ, Brown, LCWieland, Martin, J, Mitreva, M, Clardy, J, Linington, RG, Fischbach, MA
JournalCell
Volume158
Issue6
Pagination1402-14
Date Published2014 Sep 11
ISSN1097-4172
KeywordsAmino Acid Sequence, Bacteria, Biosynthetic Pathways, Gastrointestinal Tract, Humans, Metagenomics, Microbiota, Molecular Sequence Data, Mouth, Multigene Family, Peptide Biosynthesis, Nucleic Acid-Independent, Polyketides
Abstract

<p>In complex biological systems, small molecules often mediate microbe-microbe and microbe-host interactions. Using a systematic approach, we identified 3,118 small-molecule biosynthetic gene clusters (BGCs) in genomes of human-associated bacteria and studied their representation in 752 metagenomic samples from the NIH Human Microbiome Project. Remarkably, we discovered that BGCs for a class of antibiotics in clinical trials, thiopeptides, are widely distributed in genomes and metagenomes of the human microbiota. We purified and solved the structure of a thiopeptide antibiotic, lactocillin, from a prominent member of the vaginal microbiota. We demonstrate that lactocillin has potent antibacterial activity against a range of Gram-positive vaginal pathogens, and we show that lactocillin and other thiopeptide BGCs are expressed in vivo by analyzing human metatranscriptomic sequencing data. Our findings illustrate the widespread distribution of small-molecule-encoding BGCs in the human microbiome, and they demonstrate the bacterial production of drug-like molecules in humans. PAPERCLIP:</p>

DOI10.1016/j.cell.2014.08.032
Alternate JournalCell
PubMed ID25215495
PubMed Central IDPMC4164201
Grant ListR01 AI101018 / AI / NIAID NIH HHS / United States
DP2 OD007290 / OD / NIH HHS / United States
R01 DK101674 / DK / NIDDK NIH HHS / United States
T32 GM067547 / GM / NIGMS NIH HHS / United States
R21 AI101722 / AI / NIAID NIH HHS / United States
P50 GM081879 / GM / NIGMS NIH HHS / United States
U01 TW006634 / TW / FIC NIH HHS / United States