Thiol‐based switch mechanism of virulence regulator AphB modulates oxidative stress response in <i>Vibrio cholerae</i>

Liu, Zhi; Wang, Hui; Zhou, Zhigang; Ying, S.; Naseer, Nawar; Kan, Biao; Zhu, Jun

doi:10.1111/mmi.13524

Cited by 28 publications

(47 citation statements)

References 38 publications

(61 reference statements)

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“…5A). Similar results were obtained when we performed ΔahpC/⌬oxyR2 mutant competition assays using a streptomycin-treated adult mouse model (23) (Fig. 5B), suggesting that OxyR2-AhpC is not required for V. cholerae colonization, at least under the conditions tested.…”

Section: Rna Sequencing Reveals Opposing Roles For Oxyr1 and Oxyr2 Insupporting

confidence: 66%

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OxyR2 Modulates OxyR1 Activity and Vibrio cholerae Oxidative Stress Response

et al. 2017

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Bacteria have developed capacities to deal with different stresses and adapt to different environmental niches. The human pathogen Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, utilizes the transcriptional regulator OxyR to activate genes related to oxidative stress resistance, including peroxiredoxin PrxA, in response to hydrogen peroxide. In this study, we identified another OxyR homolog in V. cholerae, which we named OxyR2, and we renamed the previous OxyR OxyR1. We found that OxyR2 is required to activate its divergently transcribed gene ahpC, encoding an alkylhydroperoxide reductase, independently of H 2 O 2 . A conserved cysteine residue in OxyR2 is critical for this function. Mutation of either oxyR2 or ahpC rendered V. cholerae more resistant to H 2 O 2 . RNA sequencing analyses indicated that OxyR1-activated oxidative stress-resistant genes were highly expressed in oxyR2 mutants even in the absence of H 2 O 2 . Further genetic analyses suggest that OxyR2-activated AhpC modulates OxyR1 activity by maintaining low intracellular concentrations of H 2 O 2 . Furthermore, we showed that ΔoxyR2 and ΔahpC mutants were less fit when anaerobically grown bacteria were exposed to low levels of H 2 O 2 or incubated in seawater. These results suggest that OxyR2 and AhpC play important roles in the V. cholerae oxidative stress response.

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Section: Rna Sequencing Reveals Opposing Roles For Oxyr1 and Oxyr2 Insupporting

confidence: 66%

“…The streptomycin-treated adult mouse model was used as previously described (23,32). Briefly, 5-week-old CD-1 mice were provided with drinking water containing 0.5% (wt/vol) streptomycin and 0.5% sucrose.…”

Section: Methodsmentioning

confidence: 99%

OxyR2 Modulates OxyR1 Activity and Vibrio cholerae Oxidative Stress Response

et al. 2017

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“…These findings are also consistent with the observation that mitochondria is a major source of endogenous oxidants [38], [39]. It is reasonable to think that for eukaryotes, the peroxidase activity of Ohr may be related with detoxification of endogenous sources of hydroperoxides and might be not involved in defense towards exogenous insults of ROS, as it is currently proposed for bacteria [11], [40], [41].…”

Section: Discussionsupporting

confidence: 90%

Functional and evolutionary characterization of Ohr proteins in eukaryotes reveals many active homologs among pathogenic fungi

et al. 2017

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Ohr and OsmC proteins comprise two subfamilies within a large group of proteins that display Cys-based, thiol dependent peroxidase activity. These proteins were previously thought to be restricted to prokaryotes, but we show here, using iterated sequence searches, that Ohr/OsmC homologs are also present in 217 species of eukaryotes with a massive presence in Fungi (186 species). Many of these eukaryotic Ohr proteins possess an N-terminal extension that is predicted to target them to mitochondria. We obtained recombinant proteins for four eukaryotic members of the Ohr/OsmC family and three of them displayed lipoyl peroxidase activity. Further functional and biochemical characterization of the Ohr homologs from the ascomycete fungus Mycosphaerella fijiensis Mf_1 (MfOhr), the causative agent of Black Sigatoka disease in banana plants, was pursued. Similarly to what has been observed for the bacterial proteins, we found that: (i) the peroxidase activity of MfOhr was supported by DTT or dihydrolipoamide (dithiols), but not by β-mercaptoethanol or GSH (monothiols), even in large excess; (ii) MfOhr displayed preference for organic hydroperoxides (CuOOH and tBOOH) over hydrogen peroxide; (iii) MfOhr presented extraordinary reactivity towards linoleic acid hydroperoxides (k=3.18 (±2.13)×108 M−1 s−1). Both Cys87 and Cys154 were essential to the peroxidase activity, since single mutants for each Cys residue presented no activity and no formation of intramolecular disulfide bond upon treatment with hydroperoxides. The pKa value of the Cysp residue was determined as 5.7±0.1 by a monobromobimane alkylation method. Therefore, eukaryotic Ohr peroxidases share several biochemical features with prokaryotic orthologues and are preferentially located in mitochondria.

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“…To prolong the colonization time and include possible gut microbiota effects, we next used a modified adult mouse model (38) to examine the effects of citrate utilization on colonization. Adult mice treated with streptomycin prior to and during V. cholerae infection have been used to model in vivo pathogenesis, such as resistance to reactive oxygen/nitrogen species (18,21,22). In order to assess whether the gut microbiota affect citrate availability, we compared colonization of citrate fermentation mutants with the wild-type strain in mice that continued to have streptomycin in their drinking water after inoculation (ϩSm mice) and in mice that had streptomycin removed from their drinking water 12 h after V. cholerae inoculation (-Sm mice).…”

Section: Resultsmentioning

confidence: 99%

CitAB Two-Component System-Regulated Citrate Utilization Contributes to Vibrio cholerae Competitiveness with the Gut Microbiota

Liu

Hao

et al. 2019

Infect Immun

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Citrate is a ubiquitous compound and can be utilized by many bacterial species, including enteric pathogens, as a carbon and energy source. Genes involved in citrate utilization have been extensively studied in some enteric bacteria, such as Klebsiella pneumoniae; however, their role in pathogenesis is still not clear. In this study, we investigated citrate utilization and regulation in Vibrio cholerae, the causative agent of cholera. The putative anaerobic citrate fermentation genes in V. cholerae, consisting of citCDEFXG, citS-oadGAB, and the two-component system (TCS) genes citAB, are highly homologous to those in K. pneumoniae. Deletion analysis shows that these cit genes are essential for V. cholerae growth when citrate is the sole carbon source. The expression of citC and citS operons was dependent on citrate and CitAB, whose transcription was autorepressed and regulated by another TCS regulator, ArcA. In addition, citrate fermentation was under the control of catabolite repression. Mouse colonization experiments showed that V. cholerae can utilize citrate in vivo using the citrate fermentation pathway and that V. cholerae likely needs to compete with other members of the gut microbiota to access citrate in the gut.

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Thiol‐based switch mechanism of virulence regulator AphB modulates oxidative stress response in Vibrio cholerae

Cited by 28 publications

References 38 publications

OxyR2 Modulates OxyR1 Activity and Vibrio cholerae Oxidative Stress Response

OxyR2 Modulates OxyR1 Activity and Vibrio cholerae Oxidative Stress Response

Functional and evolutionary characterization of Ohr proteins in eukaryotes reveals many active homologs among pathogenic fungi

CitAB Two-Component System-Regulated Citrate Utilization Contributes to Vibrio cholerae Competitiveness with the Gut Microbiota

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