Hydrogen Sulfide and Reactive Sulfur Species Impact Proteome S-Sulfhydration and Global Virulence Regulation in Staphylococcus aureus

Hui Peng; Yixiang Zhang; Lauren D Palmer; Thomas E Kehl-Fie; Eric P Skaar; Jonathan C Trinidad; David P Giedroc

doi:10.1021/acsinfecdis.7b00090

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Journal article

Hydrogen Sulfide and Reactive Sulfur Species Impact Proteome S-Sulfhydration and Global Virulence Regulation in Staphylococcus aureus

Hui Peng, Yixiang Zhang, Lauren D Palmer, Thomas E Kehl-Fie, Eric P Skaar, Jonathan C Trinidad and David P Giedroc

ACS infectious diseases, Vol.3(10), pp.744-755

10/13/2017

DOI: 10.1021/acsinfecdis.7b00090

PMCID: PMC5863038

PMID: 28850209

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https://www.ncbi.nlm.nih.gov/pmc/articles/5863038View

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Abstract

Hydrogen sulfide (H S) is thought to protect bacteria from oxidative stress, but a comprehensive understanding of its function in bacteria is largely unexplored. In this study, we show that the human pathogen Staphylococcus aureus (S. aureus) harbors significant effector molecules of H S signaling, reactive sulfur species (RSS), as low molecular weight persulfides of bacillithiol, coenzyme A, and cysteine, and significant inorganic polysulfide species. We find that proteome S-sulfhydration, a post-translational modification (PTM) in H S signaling, is widespread in S. aureus. RSS levels modulate the expression of secreted virulence factors and the cytotoxicity of the secretome, consistent with an S-sulfhydration-dependent inhibition of DNA binding by MgrA, a global virulence regulator. Two previously uncharacterized thioredoxin-like proteins, denoted TrxP and TrxQ, are S-sulfhydrated in sulfide-stressed cells and are capable of reducing protein hydrodisulfides, suggesting that this PTM is potentially regulatory in S. aureus. In conclusion, our results reveal that S. aureus harbors a pool of proteome- and metabolite-derived RSS capable of impacting protein activities and gene regulation and that H S signaling can be sensed by global regulators to affect the expression of virulence factors.

Gene Expression Regulation, Bacterial - drug effects

Hydrogen Sulfide - pharmacology

Proteome

Staphylococcus aureus - metabolism

Staphylococcus aureus - pathogenicity

Sulfur - chemistry

Sulfur - pharmacology

Virulence

Details

Title: Subtitle: Hydrogen Sulfide and Reactive Sulfur Species Impact Proteome S-Sulfhydration and Global Virulence Regulation in Staphylococcus aureus
Creators: Hui Peng - Indiana University Bloomington
Yixiang Zhang - Indiana University Bloomington
Lauren D Palmer - Vanderbilt University Medical Center
Thomas E Kehl-Fie - University of Illinois Urbana-Champaign
Eric P Skaar - Vanderbilt University Medical Center
Jonathan C Trinidad - Indiana University Bloomington
David P Giedroc - Indiana University Bloomington
Resource Type: Journal article
Publication Details: ACS infectious diseases, Vol.3(10), pp.744-755
DOI: 10.1021/acsinfecdis.7b00090
PMID: 28850209
PMCID: PMC5863038
NLM abbreviation: ACS Infect Dis
ISSN: 2373-8227
eISSN: 2373-8227
Grant note: R01 AI073843 / NIAID NIH HHS T32 HL094296 / NHLBI NIH HHS F32 AI122516 / NIAID NIH HHS
Language: English
Date published: 10/13/2017
Academic Unit: Microbiology and Immunology
Record Identifier: 9984618635502771

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