期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms10710
关键词
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资金
- International Cooperative Biodiversity Groups initiative at the Fogarty International Center [U01 TW007404]
- Great Lakes Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research [U54 AI57153]
- Hans W. Vahlteich Professorship
- Army Research Office [W911NF-12-1-0059]
- National Institutes of Health [1R01GM098350]
- University of Michigan African Presidential Scholars program
Pathogenic microorganisms often have the ability to attach to a surface, building a complex matrix where they colonize to form a biofilm. This cellular superstructure can display increased resistance to antibiotics and cause serious, persistent health problems in humans. Here we describe a high-throughput in vitro screen to identify inhibitors of Acinetobacter baumannii biofilms using a library of natural product extracts derived from marine microbes. Analysis of extracts derived from Streptomyces gandocaensis results in the discovery of three peptidic metabolites (cahuitamycins A-C), with cahuitamycin C being the most effective inhibitor (IC50 = 14.5 mu M). Biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalysed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis lead to production of unnatural analogues cahuitamycins D and E of increased potency (IC50 = 8.4 and 10.5 mu M).
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