Response of Bacillus subtilis to cerulenin and acquisition of resistance

Journal of Bacteriology
Gustavo E SchujmanDiego de Mendoza

Abstract

Cerulenin is a fungal mycotoxin that potently inhibits fatty acid synthesis by covalent modification of the active site thiol of the chain-elongation subtypes of beta-ketoacyl-acyl carrier protein (ACP) synthases. The Bacillus subtilis fabF (yjaY) gene (fabF(b)) encodes an enzyme that catalyzes the condensation of malonyl-ACP with acyl-ACP to extend the growing acyl chain by two carbons. There were two mechanisms by which B. subtilis adapted to exposure to this antibiotic. First, reporter gene analysis demonstrated that transcription of the operon containing the fabF gene increased eightfold in response to a cerulenin challenge. This response was selective for the inhibition of fatty acid synthesis, since triclosan, an inhibitor of enoyl-ACP reductase, triggered an increase in fabF reporter gene expression while nalidixic acid did not. Second, spontaneous mutants arose that exhibited a 10-fold increase in the MIC of cerulenin. The mutation mapped at the B. subtilis fabF locus, and sequence analysis of the mutant fabF allele showed that a single base change resulted in the synthesis of FabF(b)[I108F]. The purified FabF(b) and FabF(b)[I108F] proteins had similar specific activities with myristoyl-ACP as the substrate. FabF(b) exh...Continue Reading

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Citations

Apr 2, 2005·Current Opinion in Microbiology·Gustavo E Schujman, Diego de Mendoza
May 10, 2003·Developmental Cell·Ethan S James, John E Cronan
Apr 16, 2002·Molecular Microbiology·R Allyn ForsythJudith W Zyskind
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Jan 27, 2006·Antimicrobial Agents and Chemotherapy·Katherine YoungJun Wang
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Jun 15, 2007·Journal of Bacteriology·Luciana PaolettiCharles O Rock
Apr 26, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jun WangSheo B Singh
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Apr 4, 2008·Molecular Microbiology·Gustavo E SchujmanDiego de Mendoza
Aug 26, 2006·The EMBO Journal·Gustavo E SchujmanDiego de Mendoza
Mar 20, 2014·The FEBS Journal·Felipe TrajtenbergGustavo E Schujman
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May 10, 2003·Developmental Cell·Gustavo E SchujmanDiego de Mendoza
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Jul 17, 2020·Molecular Microbiology·Federico MachinandiarenaDaniela Albanesi
Jun 6, 2020·Frontiers in Microbiology·Jonathan D NickelsJames G Elkins
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Jun 23, 2020·ACS Chemical Biology·Jia WangYanqiu Yuan
Mar 6, 2010·Biochemistry·Mariano A MartinezDiego de Mendoza

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