Format

Send to

Choose Destination
Biochemistry. 2016 Nov 29;55(47):6524-6534. Epub 2016 Nov 16.

Staphylococcus aureus sqr Encodes a Type II Sulfide:Quinone Oxidoreductase and Impacts Reactive Sulfur Speciation in Cells.

Author information

1
Department of Chemistry, Indiana University , Bloomington, Indiana 47405, United States.
2
Biochemistry Graduate Program, Indiana University , Bloomington, Indiana 47405, United States.
3
Laboratory for Biological Mass Spectrometry, Indiana University , Bloomington, Indiana 47405, United States.
4
Department of Molecular and Cellular Biochemistry, Indiana University , Bloomington, Indiana 47405, United States.

Abstract

Recent studies implicate hydrogen sulfide (H2S) oxidation as an important aspect of bacterial antibiotic resistance and sulfide homeostasis. The cst operon of the major human pathogen Staphylococcus aureus is induced by exogenous H2S stress and encodes enzymes involved in sulfide oxidation, including a group I flavoprotein disulfide oxidoreductase sulfide:quinone oxidoreductase (SQR). In this work, we show that S. aureus SQR catalyzes the two-electron oxidation of sodium sulfide (Na2S) into sulfane sulfur (S0) when provided flavin adenine dinucleotide and a water-soluble quinone acceptor. Cyanide, sulfite, and coenzyme A (CoA) are all capable of functioning as the S0 acceptor in vitro. This activity requires a C167-C344 disulfide bond in the resting enzyme, with the intermediacy of a C344 persulfide in the catalytic cycle, verified by mass spectrometry of sulfide-reacted SQR. Incubation of purified SQR and S. aureus CstB, a known FeII persulfide dioxygenase-sulfurtransferase also encoded by the cst operon, yields thiosulfate from sulfide, in a CoA-dependent manner, thus confirming the intermediacy of CoASSH as a product and substrate of SQR and CstB, respectively. Sulfur metabolite profiling of wild-type, Δsqr, and Δsqr::pSQR strains reveals a marked and specific elevation in endogenous levels of CoASSH and inorganic tetrasulfide in the Δsqr strain. We conclude that SQR impacts the cellular speciation of these reactive sulfur species but implicates other mechanisms not dependent on SQR in the formation of low-molecular weight thiol persulfides and inorganic polysulfides during misregulation of sulfide homeostasis.

PMID:
27806570
PMCID:
PMC5423654
DOI:
10.1021/acs.biochem.6b00714
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center