title: The Role of Bacillithiol in Gram-Positive Firmicutes.
abstract: Since the discovery and structural characterization of bacillithiol (BSH), the biochemical functions of BSH-biosynthesis enzymes (BshA/B/C) and BSH-dependent detoxification enzymes (FosB, Bst, GlxA/B) have been explored in Bacillus and Staphylococcus species. It was shown that BSH plays an important role in detoxification of reactive oxygen and electrophilic species, alkylating agents, toxins, and antibiotics. Recent Advances: More recently, new functions of BSH were discovered in metal homeostasis (Zn buffering, Fe-sulfur cluster, and copper homeostasis) and virulence control in Staphylococcus aureus. Unexpectedly, strains of the S. aureus NCTC8325 lineage were identified as natural BSH-deficient mutants. Modern mass spectrometry-based approaches have revealed the global reach of protein S-bacillithiolation in Firmicutes as an important regulatory redox modification under hypochlorite stress. S-bacillithiolation of OhrR, MetE, and glyceraldehyde-3-phosphate dehydrogenase (Gap) functions, analogous to S-glutathionylation, as both a redox-regulatory device and in thiol protection under oxidative stress.
  
  
  
  Although the functions of the bacilliredoxin (Brx) pathways in the reversal of S-bacillithiolations have been recently addressed, significantly more work is needed to establish the complete Brx reduction pathway, including the major enzyme(s), for reduction of oxidized BSH (BSSB) and the targets of Brx action in vivo.
  
  
  
  Despite the large number of identified S-bacillithiolated proteins, the physiological relevance of this redox modification was shown for only selected targets and should be a subject of future studies. In addition, many more BSH-dependent detoxification enzymes are evident from previous studies, although their roles and biochemical mechanisms require further study. This review of BSH research also pin-points these missing gaps for future research. Antioxid. Redox Signal. 28, 445-462.
authors.affiliation: 1 Department of Microbiology, Cornell University , Ithaca, New York.
authors.forename: Pete
authors.initials: P
authors.lastname: Chandrangsu
authors.affiliation: 2 Institute for Biology-Microbiology , Freie Universität Berlin, Berlin, Germany .
authors.forename: Vu Van
authors.initials: VV
authors.lastname: Loi
authors.affiliation: 2 Institute for Biology-Microbiology , Freie Universität Berlin, Berlin, Germany .
authors.forename: Haike
authors.initials: H
authors.lastname: Antelmann
authors.affiliation: 1 Department of Microbiology, Cornell University , Ithaca, New York.
authors.forename: John D
authors.initials: JD
authors.lastname: Helmann
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism; D001412:Bacillus subtilis / Q000201:enzymology / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000068536:Bacillota / Q000201:enzymology / Q000378:metabolism*; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D018384:Oxidative Stress; D013211:Staphylococcus aureus / Q000201:enzymology / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D013438:Sulfhydryl Compounds; C543521:bacillithiol; D013455:Sulfur; D003545:Cysteine; D005944:Glucosamine
keywords: BSH biosynthesis; Bacillus subtilis; S-bacillithiolation; Staphylococcus aureus; bacilliredoxin; bacillithiol; metal homeostasis; methylglyoxal