response of methicillin-resistant staphylococcus aureus to amicoumacin a耐甲氧西林金黄色葡萄球菌amicoumacin一个响应.pdfVIP

Response of Methicillin-Resistant Staphylococcus aureus to Amicoumacin A 1.¤ ´ ´ 2. 1 3 3 3 Amrita Lama , Jan Pane-Farre , Tai Chon , Anna M. Wiersma , Clarissa S. Sit , John C. Vederas , 2 1 Michael Hecker , Michiko M. Nakano * 1 Division of Environmental and Biomolecular Systems, Institute of Environmental Health, Oregon Health Science University, Beaverton, Oregon, United States of America, 2 Institute for Microbiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany, 3 Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada Abstract Amicoumacin A exhibits strong antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), hence we sought to uncover its mechanism of action. Genome-wide transcriptome analysis of S. aureus COL in response to amicoumacin A showed alteration in transcription of genes specifying several cellular processes including cell envelope turnover, cross-membrane transport, virulence, metabolism, and general stress response. The most highly induced gene was lrgA, encoding an antiholin-like product, which is induced in cells undergoing a collapse of Dy. Consistent with the notion that LrgA modulates murein hydrolase activity, COL grown in the presence of amicoumacin A showed reduced autolysis, which was primarily caused by lower hydrolase activity. To gain further insight into the mechanism of action of amicoumacin A, a whole genome comparison of wild-type COL and amicoumacin A-resistant mutants isolated by a serial passage method was carried out. Single point mutations generating cod