Importance of bacillithiol in the oxidative stress response of Staphylococcus aureus

Posada, Ana C., Kolar, Stacey L., Dusi, Renata G., Francois, Patrice, Roberts, Alexandra A., Hamilton, Chris J., Liu, George Y., and Cheung, Ambrose (2014) Importance of bacillithiol in the oxidative stress response of Staphylococcus aureus. Infection and Immunity, 82 (1). pp. 316-332.

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Abstract

In Staphylococcus aureus, the low-molecular-weight thiol called bacillithiol (BSH), together with cognate S-transferases, is believed to be the counterpart to the glutathione system of other organisms. To explore the physiological role of BSH in S. aureus, we constructed mutants with the deletion of bshA (sa1291), which encodes the glycosyltransferase that catalyzes the first step of BSH biosynthesis, and fosB (sa2124), which encodes a BSH-S-transferase that confers fosfomycin resistance, in several S. aureus strains, including clinical isolates. Mutation of fosB or bshA caused a 16- to 60-fold reduction in fosfomycin resistance in these S. aureus strains. High-pressure liquid chromatography analysis, which quantified thiol extracts, revealed some variability in the amounts of BSH present across S. aureus strains. Deletion of fosB led to a decrease in BSH levels. The fosB and bshA mutants of strain COL and a USA300 isolate, upon further characterization, were found to be sensitive to H2O2 and exhibited decreased NADPH levels compared with those in the isogenic parents. Microarray analyses of COL and the isogenic bshA mutant revealed increased expression of genes involved in staphyloxanthin synthesis in the bshA mutant relative to that in COL under thiol stress conditions. However, the bshA mutant of COL demonstrated decreased survival compared to that of the parent in human whole-blood survival assays; likewise, the naturally BSH-deficient strain SH1000 survived less well than its BSH-producing isogenic counterpart. Thus, the survival of S. aureus under oxidative stress is facilitated by BSH, possibly via a FosB-mediated mechanism, independently of its capability to produce staphyloxanthin.

Item ID: 34283
Item Type: Article (Research - C1)
ISSN: 1098-5522
Funders: National Institutes of Health (NIH), CNPq-Brazil, Biotechnology and Biological Sciences Research Council (BBSRC)
Projects and Grants: NIH R01AI91801, BBSRC grant BB/H013504/1
Date Deposited: 07 Aug 2014 02:07
FoR Codes: 06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060501 Bacteriology @ 40%
06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060502 Infectious Agents @ 50%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060104 Cell Metabolism @ 10%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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