Journal article
Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in Staphylococcus aureus
mSphere, Vol.2(3), 00082
05/01/2017
DOI: 10.1128/mSphere.00082-17
PMCID: PMC5480029
PMID: 28656172
Abstract
Staphylococcus aureus is a commensal human pathogen and a major cause of nosocomial infections. As gaseous signaling molecules, endogenous hydrogen sulfide (H2S) and nitric oxide (NO center dot) protect S. aureus from antibiotic stress synergistically, which we propose involves the intermediacy of nitroxyl (HNO). Here, we examine the effect of exogenous sulfide and HNO on the transcriptome and the formation of low-molecular-weight (LMW) thiol persulfides of bacillithiol, cysteine, and coenzyme A as representative of reactive sulfur species (RSS) in wild-type and Delta cstR strains of S. aureus. CstR is a per-and polysulfide sensor that controls the expression of a sulfide oxidation and detoxification system. As anticipated, exogenous sulfide induces the cst operon but also indirectly represses much of the CymR regulon which controls cysteine metabolism. A zinc limitation response is also observed, linking sulfide homeostasis to zinc bioavailability. Cellular RSS levels impact the expression of a number of virulence factors, including the exotoxins, particularly apparent in the Delta cstR strain. HNO, like sulfide, induces the cst operon as well as other genes regulated by exogenous sulfide, a finding that is traced to a direct reaction of CstR with HNO and to an endogenous perturbation in cellular RSS, possibly originating from disassembly of Fe-S clusters. More broadly, HNO induces a transcriptomic response to Fe overload, Cu toxicity, and reactive oxygen species and reactive nitrogen species and shares similarity with the sigB regulon. This work reveals an H2S/NO center dot interplay in S. aureus that impacts transition metal homeostasis and virulence gene expression.
IMPORTANCE Hydrogen sulfide (H2S) is a toxic molecule and a recently described gasotransmitter in vertebrates whose function in bacteria is not well understood. In this work, we describe the transcriptomic response of the major human pathogen Staphylococcus aureus to quantified changes in levels of cellular organic reactive sulfur species, which are effector molecules involved in H2S signaling. We show that nitroxyl (HNO), a recently described signaling intermediate proposed to originate from the interplay of H2S and nitric oxide, also induces changes in cellular sulfur speciation and transition metal homeostasis, thus linking sulfide homeostasis to an adaptive response to antimicrobial reactive nitrogen species.
Details
- Title: Subtitle
- Sulfide Homeostasis and Nitroxyl Intersect via Formation of Reactive Sulfur Species in Staphylococcus aureus
- Creators
- Hui Peng - Indiana University BloomingtonJiangchuan Shen - Indiana UniversityKatherine A. Edmonds - Indiana University BloomingtonJustin L. Luebke - Indiana University BloomingtonAnne K. Hickey - Indiana University BloomingtonLauren D. Palmer - Vanderbilt University Medical CenterFeng-Ming James Chang - Indiana University BloomingtonKevin A. Bruce - Indiana University BloomingtonThomas E. Kehl-Fie - University of Illinois Urbana-ChampaignEric P. Skaar - Vanderbilt University Medical CenterDavid P. Giedroc - Indiana University Bloomington
- Resource Type
- Journal article
- Publication Details
- mSphere, Vol.2(3), 00082
- Publisher
- Amer Soc Microbiology
- DOI
- 10.1128/mSphere.00082-17
- PMID
- 28656172
- PMCID
- PMC5480029
- ISSN
- 2379-5042
- eISSN
- 2379-5042
- Number of pages
- 21
- Grant note
- R01 GM030910 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R35GM118157 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) R01 GM097225; R35 GM118157; R01 AI073843; R01 AI069233; F32 AI122516; T32 HL094296; K22 AI104805; R01 AI118880 / NIH from the U.S. National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA F32AI122516 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Language
- English
- Date published
- 05/01/2017
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618525402771
Metrics
4 Record Views