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639000.8517Shotgun metagenome sequencing of a Sudanese toombak snuff tobacco: genetic attributes of a high tobacco-specific nitrosamine containing smokeless tobacco product. The most alarming aspect of the Sudanese toombak smokeless tobacco is that it contains high levels of highly toxic tobacco-specific nitrosamines (TSNAs). Understanding the microbiology of toombak is of relevance because TSNAs are an indirect result of microbial-mediated nitrate reductions. We conducted shotgun metagenomic sequencing on a toombak product for which relevant features are presented here. The microbiota was composed of over 99% Bacteria. The most abundant taxa included Actinobacteria, specifically the genera Enteractinococcus and Corynebacterium, while Firmicutes were represented by the family Bacillaceae and the genus Staphylococcus. Selected gene targets were nitrate reduction and transport, antimicrobial resistance, and other genetic transference mechanisms. Canonical nitrate reduction and transport genes (i.e. nar) were found for Enteractinococcus and Corynebacterium while various species of Staphylococcus exhibited a notable number of antimicrobial resistance and genetic transference genes. The nitrate reduction activity of the microbiota in toombak is suspected to be a contributing factor to its high levels of TSNAs. Additionally, the presence of antimicrobial resistance and transference genes could contribute to deleterious effects on oral and gastrointestinal health of the end user. Overall, the high toxicity and increased incidences of cancer and oral disease of toombak users warrants further investigation into the microbiology of toombak.202234862647
638910.8453Microbial community and functions involved in smokeless tobacco product: a metagenomic approach. Smokeless tobacco products (STPs) are attributed to oral cancer and oral pathologies in their users. STP-associated cancer induction is driven by carcinogenic compounds including tobacco-specific nitrosamines (TSNAs). The TSNAs synthesis could enhanced due to the metabolic activity (nitrate metabolism) of the microbial populations residing in STPs, but identifying microbial functions linked to the TSNAs synthesis remains unexplored. Here, we rendered the first report of shotgun metagenomic sequencing to comprehensively determine the genes of all microorganisms residing in the Indian STPs belonging to two commercial (Moist-snuff and Qiwam) and three loose (Mainpuri Kapoori, Dohra, and Gudakhu) STPs, specifically consumed in India. Further, the level of nicotine, TSNAs, mycotoxins, and toxic metals were determined to relate their presence with microbial activity. The microbial population majorly belongs to bacteria with three dominant phyla including Actinobacteria, Proteobacteria, and Firmicutes. Furthermore, the STP-linked microbiome displayed several functional genes associated with nitrogen metabolism and antibiotic resistance. The chemical analysis revealed that the Mainpuri Kapoori product contained a high concentration of ochratoxins-A whereas TSNAs and Zink (Zn) quantities were high in the Moist-snuff, Mainpuri Kapoori, and Gudakhu products. Hence, our observations will help in attributing the functional potential of STP-associated microbiome and in the implementation of cessation strategies against STPs. KEY POINTS: •Smokeless tobacco contains microbes that can assist TSNA synthesis. •Antibiotic resistance genes present in smokeless tobacco-associated bacteria. •Pathogens in STPs can cause infections in smokeless tobacco users.202438918238
50420.8434Activation of Dithiolopyrrolone Antibiotics by Cellular Reductants. Dithiolopyrrolone (DTP) natural products are broad-spectrum antimicrobial and anticancer prodrugs. The DTP structure contains a unique bicyclic ene-disulfide that once reduced in the cell, chelates metal ions and disrupts metal homeostasis. In this work we investigate the intracellular activation of the DTPs and their resistance mechanisms in bacteria. We show that the prototypical DTP holomycin is reduced by several bacterial reductases and small-molecule thiols in vitro. To understand how bacteria develop resistance to the DTPs, we generate Staphylococcus aureus mutants that exhibit increased resistance to the hybrid DTP antibiotic thiomarinol. From these mutants we identify loss-of-function mutations in redox genes that are involved in DTP activation. This work advances the understanding of how DTPs are activated and informs development of bioreductive disulfide prodrugs.202539665630
50230.8425A highly specialized flavin mononucleotide riboswitch responds differently to similar ligands and confers roseoflavin resistance to Streptomyces davawensis. Streptomyces davawensis is the only organism known to synthesize the antibiotic roseoflavin, a riboflavin (vitamin B2) analog. Roseoflavin is converted to roseoflavin mononucleotide (RoFMN) and roseoflavin adenine dinucleotide in the cytoplasm of target cells. (Ribo-)Flavin mononucleotide (FMN) riboswitches are genetic elements, which in many bacteria control genes responsible for the biosynthesis and transport of riboflavin. Streptomyces davawensis is roseoflavin resistant, and the closely related bacterium Streptomyces coelicolor is roseoflavin sensitive. The two bacteria served as models to investigate roseoflavin resistance of S. davawensis and to analyze the mode of action of roseoflavin in S. coelicolor. Our experiments demonstrate that the ribB FMN riboswitch of S. davawensis (in contrast to the corresponding riboswitch of S. coelicolor) is able to discriminate between the two very similar flavins FMN and RoFMN and shows opposite responses to the latter ligands.201222740651
50340.8400Interaction of the chromosomal Tn 551 with two thermosensitive derivatives, pS1 and p delta D, of the plasmid pI9789 in Staphylococcus aureus. The plasmid pI9789::Tn552 carries genes conferring resistance to penicillins and to cadmium, mercury and arsenate ions. The presence of Tn551 at one location in the chromosome of Staphylococcus aureus enhances the frequency of suppression of thermosensitivity of replication of the plasmids pS1 and p delta D which are derivatives of pI9789::Tn552. Bacteriophage propagated on the bacteria in which thermosensitivity of replication had been suppressed was used to transduce cadmium resistance to S. aureus PS80N. The cadmium-resistant transductants obtained carried plasmid pS1 or p delta D with a copy of Tn551 inserted into a specific site on pS1 but into several different sites on p delta D. The possible mechanisms of the suppression are discussed.19957758929
61250.8397Pathways and roles of wall teichoic acid glycosylation in Staphylococcus aureus. The thick peptidoglycan layers of Gram-positive bacteria are connected to polyanionic glycopolymers called wall teichoic acids (WTA). Pathogens such as Staphylococcus aureus, Listeria monocytogenes, or Enterococcus faecalis produce WTA with diverse, usually strain-specific structure. Extensive studies on S. aureus WTA mutants revealed important functions of WTA in cell division, growth, morphogenesis, resistance to antimicrobials, and interaction with host or phages. While most of the S. aureus WTA-biosynthetic genes have been identified it remained unclear for long how and why S. aureus glycosylates WTA with α- or β-linked N-acetylglucosamine (GlcNAc). Only recently the discovery of two WTA glycosyltransferases, TarM and TarS, yielded fundamental insights into the roles of S. aureus WTA glycosylation. Mutants lacking WTA GlcNAc are resistant towards most of the S. aureus phages and, surprisingly, TarS-mediated WTA β-O-GlcNAc modification is essential for β-lactam resistance in methicillin-resistant S. aureus. Notably, S. aureus WTA GlcNAc residues are major antigens and activate the complement system contributing to opsonophagocytosis. WTA glycosylation with a variety of sugars and corresponding glycosyltransferases were also identified in other Gram-positive bacteria, which paves the way for detailed investigations on the diverse roles of WTA modification with sugar residues.201424365646
880760.8394Dietary watermelon residue influencing the nonspecific immunity of juvenile Pseudorasbora parva. The study explored the improvement of disease resistance, non-specific immunity and anti-oxidation reactions for Pseudorasbora parva (PP) using dietary watermelon residue. The cumulative PP mortality and the pathogenic bacteria number in 15-45% groups reduced relative to those in control group (CK). Under 15-45% groups, AKP, ACP activities and akp, acp genes expression levels were increased markedly in nonspecific immunity system. Similarly, antioxidant response (SOD, CAT activities) and their genes was promoted also at 15-45% groups. Organic matter (vitamin and polyphenols) in watermelon residue improved AKP, ACP, SOD, CAT activities by increasing corresponding gene expressions. Theoretically, they could also function as stimulus signal, active center or composition to modulate enzyme activities and gene expressions. Besides, watermelon residue ameliorated NF-kB, mTOR responses pathway, and consequently suppressed Aeromonas hydrophila which augmented disease resistance.202134534653
50870.8385Insights into the chaotropic tolerance of the desert cyanobacterium Chroococcidiopsis sp. 029 (Chroococcidiopsales, Cyanobacteria). The mechanism of perchlorate resistance of the desert cyanobacterium Chroococcidiopsis sp. CCMEE 029 was investigated by assessing whether the pathways associated with its desiccation tolerance might play a role against the destabilizing effects of this chaotropic agent. During 3 weeks of growth in the presence of 2.4 mM perchlorate, an upregulation of trehalose and sucrose biosynthetic pathways was detected. This suggested that in response to the water stress triggered by perchlorate salts, these two compatible solutes play a role in the stabilization of macromolecules and membranes as they do in response to dehydration. During the perchlorate exposure, the production of oxidizing species was observed by using an oxidant-sensing fluorochrome and determining the expression of the antioxidant defense genes, namely superoxide dismutases and catalases, while the presence of oxidative DNA damage was highlighted by the over-expression of genes of the base excision repair. The involvement of desiccation-tolerance mechanisms in the perchlorate resistance of this desert cyanobacterium is interesting since, so far, chaotropic-tolerant bacteria have been identified among halophiles. Hence, it is anticipated that desert microorganisms might possess an unrevealed capability of adapting to perchlorate concentrations exceeding those naturally occurring in dry environments. Furthermore, in the endeavor of supporting future human outposts on Mars, the identified mechanisms might contribute to enhance the perchlorate resistance of microorganisms relevant for biologically driven utilization of the perchlorate-rich soil of the red planet.202438156502
52380.8384Sulfide-carbonate-mineralized functional bacterial consortium for cadmium removal in flue gas. Sulfide-carbonate-mineralized functional bacterial consortium was constructed for flue gas cadmium biomineralization. A membrane biofilm reactor (MBfR) using the bacterial consortium containing sulfate reducing bacteria (SRB) and denitrifying bacteria (DNB) was investigated for flue gas cadmium (Cd) removal. Cadmium removal efficiency achieved 90%. The bacterial consortium containing Citrobacter, Desulfocurvus and Stappia were dominated for cadmium resistance-nitrate-sulfate reduction. Under flue gas cadmium stress, ten cadmium resistance genes (czcA, czcB, czcC, czcD, cadA, cadB, cadC, cueR, copZ, zntA), and seven genes related to sulfate reduction, increased in abundance; whereas others, nine genes related to denitrification, decreased, indicating that cadmium stress was advantageous to sulfate reduction in the competition with denitrification. A bacterial consortium could capable of simultaneously cadmium resistance, sulfate reduction and denitrification. Microbial induced carbonate precipitation (MICP) and biological adsorption process would gradually yield to sulfide-mineralized process. Flue gas cadmium could transform to Cd-EPS, cadmium carbonate (CdCO(3)) and cadmium sulfide (CdS) bioprecipitate. The functional bacterial consortium was an efficient and eco-friendly bifunctional bacterial consortium for sulfide-carbonate-mineralized of cadmium. This provides a green and low-carbon advanced treatment technology using sulfide-carbonate-mineralized functional bacterial consortium for the removal of cadmium or other hazardous heavy metal contaminants in flue gas.202439019186
54890.8384Mammalian antioxidant protein complements alkylhydroperoxide reductase (ahpC) mutation in Escherichia coli. The MER5 [now called the Aop1 (antioxidant protein 1) gene] was cloned as a transiently expressed gene of murine erythroleukaemia (MEL) cell differentiation and its antisense expression inhibited differentiation of MEL cells. We found that the Aop1 gene shows significant nucleotide sequence similarity to the gene coding for the C22 subunit of Salmonella typhimurium alkylhydroperoxide reductase, which is also found in other bacteria, suggesting it functions as an antioxidant protein. Expression of the Aop1 gene product in E. coli deficient in the C22-subunit gene rescued resistance of the bacteria to alkylhydroperoxide. The human and mouse Aop1 genes are highly conserved, and they mapped to the regions syntenic between mouse and human chromosomes. Sequence comparisons with recently cloned mammalian Aop1 homologues suggest that these genes consist of a family that is responsible for regulation of cellular proliferation, differentiation and antioxidant functions.19957733872
611100.8383The Staphylococcus aureus FASII bypass escape route from FASII inhibitors. Antimicrobials targeting the fatty acid synthesis (FASII) pathway are being developed as alternative treatments for bacterial infections. Emergence of resistance to FASII inhibitors was mainly considered as a consequence of mutations in the FASII target genes. However, an alternative and efficient anti-FASII resistance strategy, called here FASII bypass, was uncovered. Bacteria that bypass FASII incorporate exogenous fatty acids in membrane lipids, and thus dispense with the need for FASII. This strategy is used by numerous Gram-positive low GC % bacteria, including streptococci, enterococci, and staphylococci. Some bacteria repress FASII genes once fatty acids are available, and "constitutively" shift to FASII bypass. Others, such as the major pathogen Staphylococcus aureus, can undergo high frequency mutations that favor FASII bypass. This capacity is particularly relevant during infection, as the host supplies the fatty acids needed for bacteria to bypass FASII and thus become resistant to FASII inhibitors. Screenings for anti-FASII resistance in the presence of exogenous fatty acids confirmed that FASII bypass confers anti-FASII resistance among clinical and veterinary isolates. Polymorphisms in S. aureus FASII initiation enzymes favor FASII bypass, possibly by increasing availability of acyl-carrier protein, a required intermediate. Here we review FASII bypass and consequences in light of proposed uses of anti-FASII to treat infections, with a focus on FASII bypass in S. aureus.201728728970
3110.8382Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway that does not use protoporphyrin. It has been generally accepted that biosynthesis of protoheme (heme) uses a common set of core metabolic intermediates that includes protoporphyrin. Herein, we show that the Actinobacteria and Firmicutes (high-GC and low-GC Gram-positive bacteria) are unable to synthesize protoporphyrin. Instead, they oxidize coproporphyrinogen to coproporphyrin, insert ferrous iron to make Fe-coproporphyrin (coproheme), and then decarboxylate coproheme to generate protoheme. This pathway is specified by three genes named hemY, hemH, and hemQ. The analysis of 982 representative prokaryotic genomes is consistent with this pathway being the most ancient heme synthesis pathway in the Eubacteria. Our results identifying a previously unknown branch of tetrapyrrole synthesis support a significant shift from current models for the evolution of bacterial heme and chlorophyll synthesis. Because some organisms that possess this coproporphyrin-dependent branch are major causes of human disease, HemQ is a novel pharmacological target of significant therapeutic relevance, particularly given high rates of antimicrobial resistance among these pathogens.201525646457
501120.8382Centromere anatomy in the multidrug-resistant pathogen Enterococcus faecium. Multidrug-resistant variants of the opportunistic human pathogen Enterococcus have recently emerged as leading agents of nosocomial infection. The acquisition of plasmid-borne resistance genes is a driving force in antibiotic-resistance evolution in enterococci. The segregation locus of a high-level gentamicin-resistance plasmid, pGENT, in Enterococcus faecium was identified and dissected. This locus includes overlapping genes encoding PrgP, a member of the ParA superfamily of segregation proteins, and PrgO, a site-specific DNA binding homodimer that recognizes the cenE centromere upstream of prgPO. The centromere has a distinctive organization comprising three subsites, CESII separates CESI and CESIII, each of which harbors seven TATA boxes spaced by half-helical turns. PrgO independently binds both CESI and CESIII, but with different affinities. The topography of the complex was probed by atomic force microscopy, revealing discrete PrgO foci positioned asymmetrically at the CESI and CESIII subsites. Bending analysis demonstrated that cenE is intrinsically curved. The organization of the cenE site and of certain other plasmid centromeres mirrors that of yeast centromeres, which may reflect a common architectural requirement during assembly of the mitotic apparatus in yeast and bacteria. Moreover, segregation modules homologous to that of pGENT are widely disseminated on vancomycin and other resistance plasmids in enterococci. An improved understanding of segrosome assembly may highlight new interventions geared toward combating antibiotic resistance in these insidious pathogens.200818245388
8128130.8382Recognize and assessment of key host humic-reducing microorganisms of antibiotic resistance genes in different biowastes composts. Humic-reducing microorganisms (HRMs) can utilize humic substance as terminal electron mediator promoting the bioremediation of contaminate, which is ubiquitous in composts. However, the impacts of HRMs on antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in composts and different HRMs community composition following the types of biowastes effected the spread of ARGs have not been investigated. Herein, the dynamics and mobility of ARGs and HRMs during protein-, lignocellulose- and lignin-rich composting were investigated. Result show that ARGs change significantly at the thermophilic phase, and the relative abundance of most ARGs increase during composting. Seven groups of HRMs communities are classified as primary host HRMs of ARGs, and most host HRMs groups from protein-rich composts. Conclusively, regulating methods for inhibiting ARGs spread for different composts are proposed. HRMs show a higher ARGs dissemination capacity in protein-rich composts than lignocellulose- and lignin-rich composts, but the spread of ARGs can be inhibited by regulate physicochemical parameters in protein-rich composts. In contrary, most HRMs have inhibitory effects on ARGs spread in lignocellulose- and lignin-rich composts, and those HRMs can be used as a new agent that inhibits the spread of ARGs. Our results can help in understanding the potential risk spread of ARGs by inoculating functional bacteria derived from different biowastes composts for environmental remediation, given their expected importance to developing a classification-oriented approach for composting different biowastes.202234600985
8186140.8377Tumor-infiltrating bacteria disrupt cancer epithelial cell interactions and induce cell-cycle arrest. Tumor-infiltrating bacteria are increasingly recognized as modulators of cancer progression and therapy resistance. We describe a mechanism by which extracellular intratumoral bacteria, including Fusobacterium, modulate cancer epithelial cell behavior. Spatial imaging and single-cell spatial transcriptomics show that these bacteria predominantly localize extracellularly within tumor microniches of colorectal and oral cancers, characterized by reduced cell density, transcriptional activity, and proliferation. In vitro, Fusobacterium nucleatum disrupts epithelial contacts, inducing G0-G1 arrest and transcriptional quiescence. This state confers 5-fluorouracil resistance and remodels the tumor microenvironment. Findings were validated by live-cell imaging, spatial profiling, mouse models, and a 52-patient colorectal cancer cohort. Transcriptomics reveals downregulation of cell cycle, transcription, and antigen presentation genes in bacteria-enriched regions, consistent with a quiescent, immune-evasive phenotype. In an independent rectal cancer cohort, high Fusobacterium burden correlates with reduced therapy response. These results link extracellular bacteria to cancer cell quiescence and chemoresistance, highlighting microbial-tumor interactions as therapeutic targets.202541106380
8672150.8367Pangenomic and functional investigations for dormancy and biodegradation features of an organic pollutant-degrading bacterium Rhodococcus biphenylivorans TG9. Environmental bacteria contain a wealth of untapped potential in the form of biodegradative genes. Leveraging this potential can often be confounded by a lack of understanding of fundamental survival strategies, like dormancy, for environmental stress. Investigating bacterial dormancy-to-degradation relationships enables improvement of bioremediation. Here, we couple genomic and functional assessment to provide context for key attributes of the organic pollutant-degrading strain Rhodococcus biphenylivorans TG9. Whole genome sequencing, pangenome analysis and functional characterization were performed to elucidate important genes and gene products, including antimicrobial resistance, dormancy, and degradation. Rhodococcus as a genus has strong potential for degradation and dormancy, which we demonstrate using R. biphenylivorans TG9 as a model. We identified four Resuscitation-promoting factor (Rpf) encoding genes in TG9 involved in dormancy and resuscitation. We demonstrate that R. biphenylivorans TG9 grows on fourteen typical organic pollutants, and exhibits a robust ability to degrade biphenyl and several congeners of polychlorinated biphenyls. We further induced TG9 into a dormant state and demonstrated pronounced differences in morphology and activity. Together, these results expand our understanding of the genus Rhodococcus and the relationship between dormancy and biodegradation in the presence of environmental stressors.202234688761
8425160.8365Carotenoid biosynthesis in extremophilic Deinococcus-Thermus bacteria. Bacteria from the phylum Deinococcus-Thermus are known for their resistance to extreme stresses including radiation, oxidation, desiccation and high temperature. Cultured Deinococcus-Thermus bacteria are usually red or yellow pigmented because of their ability to synthesize carotenoids. Unique carotenoids found in these bacteria include deinoxanthin from Deinococcus radiodurans and thermozeaxanthins from Thermus thermophilus. Investigations of carotenogenesis will help to understand cellular stress resistance of Deinococcus-Thermus bacteria. Here, we discuss the recent progress toward identifying carotenoids, carotenoid biosynthetic enzymes and pathways in some species of Deinococcus-Thermus extremophiles. In addition, we also discuss the roles of carotenoids in these extreme bacteria.201020832321
549170.8363Extracytoplasmic function sigma factor σ(D) confers resistance to environmental stress by enhancing mycolate synthesis and modifying peptidoglycan structures in Corynebacterium glutamicum. Mycolates are α-branched, β-hydroxylated, long-chain fatty acid specifically synthesized in bacteria in the suborder Corynebacterineae of the phylum Actinobacteria. They form an outer membrane, which functions as a permeability barrier and confers pathogenic mycobacteria to resistance to antibiotics. Although the mycolate biosynthetic pathway has been intensively studied, knowledge of transcriptional regulation of genes involved in this pathway is limited. Here, we report that the extracytoplasmic function sigma factor σ(D) is a key regulator of the mycolate synthetic genes in Corynebacterium glutamicum in the suborder. Chromatin immunoprecipitation with microarray analysis detected σ(D) -binding regions in the genome, establishing a consensus promoter sequence for σ(D) recognition. The σ(D) regulon comprised acyl-CoA carboxylase subunits, acyl-AMP ligase, polyketide synthase and mycolyltransferases; they were involved in mycolate synthesis. Indeed, deletion or overexpression of sigD encoding σ(D) modified the extractable mycolate amount. Immediately downstream of sigD, rsdA encoded anti-σ(D) and was under the control of a σ(D) -dependent promoter. Another σ(D) regulon member, l,d-transpeptidase, conferred lysozyme resistance. Thus, σ(D) modifies peptidoglycan cross-linking and enhances mycolate synthesis to provide resistance to environmental stress.201829148103
8543180.8363Soil bacteria, genes, and metabolites stimulated during sulfur cycling and cadmium mobilization under sodium sulfate stress. Sodium sulfate stress is known to improve cadmium (Cd) mobilization in soil and microbial sulfur oxidation, Cd resistance, and the accumulation of stress tolerance-associated metabolites has been correlated with increased soil Cd availability and toxicity. In this study, aerobic soil microcosms with Cd-contamination were stimulated with sodium sulfate to investigate its effects on soil microbial community structure, functional genes, and associated metabolite profiles. Metagenomic analysis revealed that sulfur oxidizing and Cd-resistant bacteria carried gene clusters encoding sox, dsr, and sqr genes, and znt, czc, and cad genes, respectively. Exposure to sodium sulfate resulted in the reprogram of soil metabolites. In particular, intensification of sulfur metabolism triggered an up-regulation in the tricarboxylic acid (TCA) cycle, which promoted the secretion of carboxylic acids and their precursors by soil bacteria. The accumulation of organic acids induced in response to high sodium sulfate dosages potentially drove an observed increase in Cd mobility. Pseudomonas and Erythrobacter spp. exhibited a high capacity for adaptation to heavy metal- or sulfur-induced stress, evident by an increased abundance of genes and metabolites for sulfur cycling and Cd resistance. These results provide valuable insights towards understanding the microbial mechanisms of sulfur transformation and Cd dissolution under saline stress.202134214562
543190.8359OxyR2 Modulates OxyR1 Activity and Vibrio cholerae Oxidative Stress Response. 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.201728138024