Hydrogen Sulfide Signaling and Enzymology

Walsh, Brenna J. C.; Brito, José A.; Giedroc, D.P.

doi:10.1016/b978-0-12-409547-2.14699-2

Cited by 3 publications

(4 citation statements)

References 250 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SQR catalyzes the two-electron oxidation of H 2 S to sulfane sulfur fixed as organic and inorganic per-and polysulfides ( Fig. 4B), concomitant with reduction of the quinone pool (126). This enzyme may well provide a source of electrons for the alternative cytochrome bd oxidase in organisms that encode this alternate oxidase, analogous to that observed for SQR with complex III/IV when the concentration of H 2 S is low ( Fig.…”

Section: Biogenesis and Clearance Of Organic Rss In Bacteriamentioning

confidence: 77%

“…Major structural classes of sulfurtransferases (STRs) adopt either a rhodanese or TusA (tRNA 2-thiouridine-synthesizing protein A)-like fold (126) and harbor an active-site cysteine that is known or projected to function in interdomain or intermolecular persulfide transfer, termed transsulfuration ( Fig. 4C) (127).…”

Section: Sulfurtransferasesmentioning

confidence: 99%

“…S. aureus CstR regulates the cst operon encoding a multidomain STR (CstA), a PRF (CstB), and a type II SQR, rather analogous to the well-studied mitochondrial sulfide detoxification system (76,123,135,139). The enzymes encoded by the S. aureus cst operon oxidize sulfide to thiosulfate via persulfide intermediates and have been extensively reviewed elsewhere (126). Recently, we characterized CstR from a second human pathogen E. faecalis that regulates a cst-like operon encoding two orphan STRs and a CoAPR (Fig.…”

Section: Cstrmentioning

confidence: 99%

See 2 more Smart Citations

H2S and reactive sulfur signaling at the host-bacterial pathogen interface

Walsh

Giedroc

2020

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Bacterial pathogens that cause invasive disease in the vertebrate host must adapt to host efforts to cripple their viability. Major host insults are reactive oxygen and reactive nitrogen species as well as cellular stress induced by antibiotics. Hydrogen sulfide (H2S) is emerging as an important player in cytoprotection against these stressors, which may well be attributed to downstream more oxidized sulfur species termed reactive sulfur species (RSS). In this review, we summarize recent work that suggests that H2S/RSS impacts bacterial survival in infected cells and animals. We discuss the mechanisms of biogenesis and clearance of RSS in the context of a bacterial H2S/RSS homeostasis model, and the bacterial transcriptional regulatory proteins that act as “sensors” of cellular RSS that maintain H2S/RSS homeostasis. In addition, we cover fluorescence imaging- and mass spectrometry-based approaches used to detect and quantify RSS in bacterial cells. Lastly, we discuss proteome persulfidation (S-sulfuration) as potential mediators of H2S/RSS signaling in bacteria in the context of the writer-reader-eraser paradigm, and progress toward ascribing regulatory significance to this widespread post-translational modification.

show abstract

Section: Biogenesis and Clearance Of Organic Rss In Bacteriamentioning

confidence: 77%

Section: Sulfurtransferasesmentioning

confidence: 99%

Section: Cstrmentioning

confidence: 99%

See 1 more Smart Citation

H2S and reactive sulfur signaling at the host-bacterial pathogen interface

Walsh

Giedroc

2020

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Bacteria maintain H 2 S/RSS homeostasis by expressing persulfide-sensing transcriptional regulators which regulons generally encode for a subset of common downstream H 2 S detoxification genes (50, 51). The mechanisms that allow H 2 S/RSS homeostasis in bacteria have been described for several human pathogens (34, 37, 48, 52), however little is known about how V. cholerae responds to increasing H 2 S/RSS and how these reactive species affect pathogen metabolism and, ultimately, gut colonization.…”

Section: Introductionmentioning

confidence: 99%

Increased intracellular persulfide levels attenuate HlyU-mediated hemolysin transcriptional activation inVibrio cholerae

Diez

Antelo

Dalia

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

In vertebrates, host's immune system and resident commensal bacteria deploy a range of highly reactive small molecules that provide a barrier against microbial pathogens, including those known to induce oxidative and sulfide stress. Gut pathogens, such as Vibrio cholerae, sense and respond to these stressors by modulating the expression of exotoxins that are crucial for colonization. Here, we employ mass-spectrometry-based profiling, metabolomics, expression assays and biophysical approaches to show that transcriptional activation of the hemolysin gene hlyA in V. cholerae is regulated by intracellular RSS (reactive sulfur species, specifically sulfane sulfur). We first report a sequence similarity network analysis of the arsenic repressor (ArsR) superfamily of transcriptional regulators where RSS and ROS (reactive oxygen species) sensors segregate into distinct clusters. We show that HlyU, transcriptional activator of hlyA in V. cholerae, belongs to the RSS-sensing cluster and readily reacts with organic persulfides, showing no reactivity and remaining DNA-bound following treatment with various ROS in vitro, including H2O2. Surprisingly, in V. cholerae cell cultures both sulfide and peroxide treatment downregulate HlyU-dependent transcriptional activation of hlyA. However, RSS metabolite profiling showed that both sulfide and peroxide treatment raise the endogenous inorganic sulfide and disulfide levels to a similar extent, accounting for this crosstalk, and confirming that V. cholerae attenuates HlyU-mediated activation of hlyA in a specific response to intracellular RSS. These findings provide new evidence that gut pathogens may harness RSS-sensing as an evolutionary adaptation that allows them to overcome the gut inflammatory response by modulating the expression of exotoxins.

show abstract

The Response of Acinetobacter baumannii to Hydrogen Sulfide Reveals Two Independent Persulfide-Sensing Systems and a Connection to Biofilm Regulation

Walsh

Wang

Edmonds

et al. 2020

mBio

Self Cite

View full text Add to dashboard Cite

Acinetobacter baumannii is an opportunistic nosocomial pathogen that is the causative agent of several serious infections in humans, including pneumonia, sepsis, and wound and burn infections. A. baumannii is also capable of forming proteinaceous biofilms on both abiotic and epithelial cell surfaces. Here, we investigate the response of A. baumannii toward sodium sulfide (Na2S), known to be associated with some biofilms at oxic/anoxic interfaces. The addition of exogenous inorganic sulfide reveals that A. baumannii encodes two persulfide-sensing transcriptional regulators, a primary σ54-dependent transcriptional activator (FisR), and a secondary system controlled by the persulfide-sensing biofilm growth-associated repressor (BigR), which is only induced by sulfide in a fisR deletion strain. FisR activates an operon encoding a sulfide oxidation/detoxification system similar to that characterized previously in Staphylococcus aureus, while BigR regulates a secondary persulfide dioxygenase (PDO2) as part of yeeE-yedE-pdo2 sulfur detoxification operon, found previously in Serratia spp. Global S-sulfuration (persulfidation) mapping of the soluble proteome reveals 513 persulfidation targets well beyond FisR-regulated genes and includes five transcriptional regulators, most notably the master biofilm regulator BfmR and a poorly characterized catabolite regulatory protein (Crp). Both BfmR and Crp are well known to impact biofilm formation in A. baumannii and other organisms, respectively, suggesting that persulfidation of these regulators may control their activities. The implications of these findings on bacterial sulfide homeostasis, persulfide signaling, and biofilm formation are discussed. IMPORTANCE Although hydrogen sulfide (H2S) has long been known as a respiratory poison, recent reports in numerous bacterial pathogens reveal that H2S and more downstream oxidized forms of sulfur collectedly termed reactive sulfur species (RSS) function as antioxidants to combat host efforts to clear the infection. Here, we present a comprehensive analysis of the transcriptional and proteomic response of A. baumannii to exogenous sulfide as a model for how this important human pathogen manages sulfide/RSS homeostasis. We show that A. baumannii is unique in that it encodes two independent persulfide sensing and detoxification pathways that govern the speciation of bioactive sulfur in cells. The secondary persulfide sensor, BigR, impacts the expression of biofilm-associated genes; in addition, we identify two other transcriptional regulators known or projected to regulate biofilm formation, BfmR and Crp, as highly persulfidated in sulfide-exposed cells. These findings significantly strengthen the connection between sulfide homeostasis and biofilm formation in an important human pathogen.

show abstract

Hydrogen Sulfide Signaling and Enzymology

Cited by 3 publications

References 250 publications

H2S and reactive sulfur signaling at the host-bacterial pathogen interface

H2S and reactive sulfur signaling at the host-bacterial pathogen interface

Increased intracellular persulfide levels attenuate HlyU-mediated hemolysin transcriptional activation inVibrio cholerae

The Response of Acinetobacter baumannii to Hydrogen Sulfide Reveals Two Independent Persulfide-Sensing Systems and a Connection to Biofilm Regulation

Contact Info

Product

Resources

About