title: Biophysical features of bacillithiol, the glutathione surrogate of Bacillus subtilis and other firmicutes.
abstract: Bacillithiol (BSH) is the major low-molecular-weight (LMW) thiol in many low-G+C Gram-positive bacteria (Firmicutes). Evidence now emerging suggests that BSH functions as an important LMW thiol in redox regulation and xenobiotic detoxification, analogous to what is already known for glutathione and mycothiol in other microorganisms. The biophysical properties and cellular concentrations of such LMW thiols are important determinants of their biochemical efficiency both as biochemical nucleophiles and as redox buffers. Here, BSH has been characterised and compared with other LMW thiols in terms of its thiol pKa , redox potential and thiol-disulfide exchange reactivity. Both the thiol pKa and the standard thiol redox potential of BSH are shown to be significantly lower than those of glutathione whereas the reactivities of the two compounds in thiol-disulfide reactions are comparable. The cellular concentration of BSH in Bacillus subtilis varied over different growth phases and reached up to 5 mM, which is significantly greater than previously observed from single measurements taken during mid-exponential growth. These results demonstrate that the biophysical characteristics of BSH are distinctively different from those of GSH and that its cellular concentrations can reach levels much higher than previously reported.
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ (UK).
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Sharma
authors.forename: Miriam
authors.initials: M
authors.lastname: Arbach
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: Roberts
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Macdonald
authors.forename: Murree
authors.initials: M
authors.lastname: Groom
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hamilton
mesh_terms: D000588:Amines / Q000737:chemistry; D001412:Bacillus subtilis / Q000737:chemistry* / Q000378:metabolism; D002264:Carboxylic Acids / Q000737:chemistry; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D007700:Kinetics; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000588:Amines; D002264:Carboxylic Acids; D013438:Sulfhydryl Compounds; C543521:bacillithiol; D005978:Glutathione; D003545:Cysteine; D005944:Glucosamine
keywords: NMR spectroscopy; ionization potentials; redox chemistry; thiol-disulfide exchange; thiols