title: Distribution and infection-related functions of bacillithiol in Staphylococcus aureus.
abstract: Bacillithiol (Cys-GlcN-malate, BSH) serves as a major low molecular weight thiol in low GC Gram-positive bacteria including Bacillus species and a variety of Staphylococcus aureus strains. These bacteria do not produce glutathione (GSH). In this study, HPLC analyses were used to determine BSH levels in different S. aureus strains. Furthermore, the role of BSH in the resistance against oxidants and antibiotics and its function in virulence was investigated. We and others (Newton, G.L., Fahey, R.C., Rawat, M., 2012. Microbiology 158, 1117-1126) found that BSH is not produced by members of the S. aureus NCTC8325 lineage, such as strains 8325-4 and SH1000. Using bioinformatics we show that the BSH-biosynthetic gene bshC is disrupted by an 8-bp duplication in S. aureus NCTC8325. The functional bshC-gene from BSH-producing S. aureus Newman (NWMN_1087) was expressed in S. aureus 8325-4 to reconstitute BSH-synthesis. Comparison of the BSH-producing and BSH-minus strains revealed higher resistance of the BSH-producing strain against the antibiotic fosfomycin and the oxidant hypochlorite but not against hydrogen peroxide or diamide. In addition, a higher bacterial load of the BSH-producing strain was detected in human upper-airway epithelial cells and murine macrophages. This indicates a potential role of BSH in protection of S. aureus during infection.
authors.affiliation: Institute of Microbiology, Ernst-Moritz-Arndt-University of Greifswald, 17487 Greifswald, Germany.
authors.forename: Dierk-Christoph
authors.initials: DC
authors.lastname: Pöther
authors.forename: Philipp
authors.initials: P
authors.lastname: Gierok
authors.forename: Manuela
authors.initials: M
authors.lastname: Harms
authors.forename: Jörg
authors.initials: J
authors.lastname: Mostertz
authors.forename: Falko
authors.initials: F
authors.lastname: Hochgräfe
authors.forename: Haike
authors.initials: H
authors.lastname: Antelmann
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hamilton
authors.forename: Ilya
authors.initials: I
authors.lastname: Borovok
authors.forename: Michael
authors.initials: M
authors.lastname: Lalk
authors.forename: Yair
authors.initials: Y
authors.lastname: Aharonowitz
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000975:Antioxidants; D058491:Bacterial Load; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics; D003958:Diamide / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D004847:Epithelial Cells / Q000382:microbiology; D005578:Fosfomycin / Q000494:pharmacology; D015870:Gene Expression; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D016877:Oxidants / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D037521:Virulence Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D016877:Oxidants; D037521:Virulence Factors; C543521:bacillithiol; D003958:Diamide; D005578:Fosfomycin; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D003545:Cysteine; D005944:Glucosamine