Redox regulation in host-pathogen interactions: thiol switches and beyond

Varatnitskaya, Marharyta; Degrossoli, Adriana; Leichert, Lars I.

doi:10.1515/hsz-2020-0264

Cited by 21 publications

(15 citation statements)

References 134 publications

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“…Post-translational modification and activation of chaperones are part of strategies developed by bacteria to protect proteins against oxidative damages [ 56 ]. DnaK and DnaJ are components of the DnaK/DnaJ/GrpE chaperone system involved in refolding proteins to their native conformation [ 57 ].…”

Section: Resultsmentioning

confidence: 99%

Cysteine Proteome Reveals Response to Endogenous Oxidative Stress in Bacillus cereus

Hamitouche

Armengaud

Dedieu

et al. 2021

IJMS

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At the end of exponential growth, aerobic bacteria have to cope with the accumulation of endogenous reactive oxygen species (ROS). One of the main targets of these ROS is cysteine residues in proteins. This study uses liquid chromatography coupled to high-resolution tandem mass spectrometry to detect significant changes in protein abundance and thiol status for cysteine-containing proteins from Bacillus cereus during aerobic exponential growth. The proteomic profiles of cultures at early-, middle-, and late-exponential growth phases reveals that (i) enrichment in proteins dedicated to fighting ROS as growth progressed, (ii) a decrease in both overall proteome cysteine content and thiol proteome redox status, and (iii) changes to the reduced thiol status of some key proteins, such as the transition state transcriptional regulator AbrB. Taken together, our data indicate that growth under oxic conditions requires increased allocation of protein resources to attenuate the negative effects of ROS. Our data also provide a strong basis to understand the response mechanisms used by B. cereus to deal with endogenous oxidative stress.

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Section: Resultsmentioning

confidence: 99%

Cysteine Proteome Reveals Response to Endogenous Oxidative Stress in Bacillus cereus

Hamitouche

Armengaud

Dedieu

et al. 2021

IJMS

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“…1A-C). HOCl is well known for its high microbicidal activity (16,51,60), which explains its role as the active ingredient in household bleach, one of the most commonly used disinfectants in medical, industrial, and domestic settings (18). The oxidant rapidly reacts with a wide range of biological molecules including DNA, lipids, and proteins (9,15).…”

Section: Discussionmentioning

confidence: 99%

Redox-mediated inactivation of the transcriptional repressor C3600 makes uropathogenicEscherichia coliexquisitely resistant to reactive chlorine species

Sultana¹,

LeDoux²,

Crompton³

et al. 2021

Preprint

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The ability to overcome stressful environments is critical for pathogen survival in the host. One challenge for bacteria is the exposure to reactive chlorine species (RCS), which are generated by innate immune cells as critical part of the oxidative burst. Hypochlorous acid (HOCl) is the most potent antimicrobial RCS and associated with extensive macromolecular damage in the phagocytized pathogen. However, bacteria have evolved defense strategies to alleviate the effects of HOCl-mediated damage. Among these are RCS-sensing transcriptional regulators that control the expression of HOCl-protective genes under non- and HOCl stress. Uropathogenic Escherichia coli (UPEC), the major causative agent of urinary tract infections (UTIs), is particularly exposed to infiltrating neutrophils during pathogenesis, however, their responses to and defenses of HOCl are still completely unexplored. Here, we present evidence that UPEC strains tolerate higher levels of HOCl and are better protected from neutrophil-mediated killing compared to other E. coli. Transcriptomic analysis of HOCl-stressed UPEC revealed the upregulation of an operon consisting of three genes, one of which encodes the transcriptional regulator C3600. We identified C3600 as a HOCl-sensing transcriptional repressor, which, under non-stress conditions, is bound to the operator and represses the expression of its target genes. During HOCl exposure, however, the repressor forms reversible intermolecular disulfide bonds and dissociates from the DNA resulting in the de-repression of the operon. Deletion of one of the target genes renders UPEC significantly more susceptible to HOCl indicating that the HOCl-mediated induction of the regulon plays a major role for UPEC’s HOCl resistance.

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“…Based on all the findings cited above, it appears that a Met-redox switch might play a role in HypV sensing mechanism, in sharp homology with the HOCl-specific transcription factor HypT. 17 making the reaction much slower and requiring higher concentration of H 2 O 2 that might not be physiological. One should note that we didn't bring direct proof of in vivo Met oxidation in HypV.…”

Section: Discussionmentioning

confidence: 99%

“…Our next goal was to investigate the molecular mechanism by which YedV senses HOCl. HOCl has been shown to modify proteins via the oxidation of sulfur-containing compounds, such as cysteine and methionine 17 . Both residues have the highest degree of reactivity towards HOCl.…”

Section: Positions Met72 and Met153 Are Important For Yedv Activitymentioning

confidence: 99%

HypVW is an HOCl-Sensing Two Component System in Escherichia coli

Hajj

Henry

Vergnes

et al. 2021

Preprint

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Two component systems (TCS) are signalling pathways that allow bacterial cells to sense, respond and adapt to fluctuating environments. Among the classical TCS of Escherichia coli, YedVW has been recently showed to be involved in the regulation of msrPQ, encoding for the periplasmic methionine sulfoxide reductase system. In this study, we demonstrate that hypochlorous acid (HOCl) induces the expression of msrPQ in a YedVW dependant manner, whereas H2O2, NO and paraquat (a superoxide generator) do not. Therefore, YedV appears to be an HOCl-sensing histidine kinase. Based on this finding, we proposed to rename this system HypVW. Moreover, using a directed mutagenesis approach, we show that Met residues located in the periplasmic loop of HypV (formerly YedV) are important for its activity. Given that HOCl oxidizes preferentially Met residues, we bring evidences that HypV could be activated via the reversible oxidation of its methionine residues, thus conferring to MsrPQ a role in switching HypVW off. Based on these results, we propose that the activation of HypV by HOCl could occur through a Met redox switch. HypVW appears to be the first characterized TCS able to detect HOCl in E. coli. This study represents an important step in understanding the mechanisms of reactive chlorine species resistance in prokaryotes.

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Redox regulation in host-pathogen interactions: thiol switches and beyond

Cited by 21 publications

References 134 publications

Cysteine Proteome Reveals Response to Endogenous Oxidative Stress in Bacillus cereus

Cysteine Proteome Reveals Response to Endogenous Oxidative Stress in Bacillus cereus

Redox-mediated inactivation of the transcriptional repressor C3600 makes uropathogenicEscherichia coliexquisitely resistant to reactive chlorine species

HypVW is an HOCl-Sensing Two Component System in Escherichia coli

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