Fusidic acid-resistant mutants of Salmonella enterica serovar typhimurium have low levels of heme and a reduced rate of respiration and are sensitive to oxidative stress

Antimicrobial Agents and Chemotherapy
Mirjana MacvaninD Hughes

Abstract

Mutations in the translation elongation factor G (EF-G) make Salmonella enterica serovar Typhimurium resistant to the antibiotic fusidic acid. Fus(r) mutants are hypersensitive to oxidative stress and rapidly lose viability in the presence of hydrogen peroxide. We show that this phenotype is associated with reduced activity of two catalase enzymes, HPI (a bifunctional catalase-hydroperoxidase) and HPII (a monofunctional catalase). These catalases require the iron-binding cofactor heme for their activity. Fus(r) mutants have a reduced rate of transcription of hemA, a gene whose product catalyzes the first committed step in heme biosynthesis. Hypersensitivity of Fus(r) mutants to hydrogen peroxide is abolished by the presence of delta-aminolevulinic acid, the precursor of heme synthesis, in the growth media and by the addition of glutamate or glutamine, amino acids required for the first step in heme biosynthesis. Fluorescence measurements show that the level of heme in a Fus(r) mutant is significantly lower than it is in the wild type. Heme is also an essential cofactor of cytochromes in the electron transport chain of respiration. We found that the rate of respiration is reduced significantly in Fus(r) mutants. Sequestration of...Continue Reading

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Citations

Mar 9, 2010·Nature Reviews. Microbiology·Dan I Andersson, Diarmaid Hughes
Apr 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·Annika I NilssonDan I Andersson
Mar 3, 2009·Proteomics·María Fernández-ReyesLuis Rivas
Mar 24, 2006·Molecular Microbiology·Tanel Tenson, Alexander Mankin
Apr 11, 2015·Evolutionary Applications·Anita H MelnykRees Kassen
Aug 8, 2006·Current Opinion in Microbiology·Dan I Andersson
May 23, 2006·Microbes and Infection·Qijing ZhangSophie Payot
Jun 7, 2005·FEMS Microbiology Letters·Mirjana Macvanin, Diarmaid Hughes
Mar 28, 2012·Nature Reviews. Microbiology·Thomas HindréDominique Schneider

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