The VicRK System of <i>Streptococcus mutans</i> Responds to Oxidative Stress

Deng, Dongsheng; Liu, M.J.; Cate, J.M. ten

doi:10.1177/154405910708600705

Cited by 73 publications

(68 citation statements)

References 25 publications

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“…The VicK mutant's impaired cell shape, its size, and its enhanced sensitivity to environmental stresses (8,10,47,48) suggest an important role for VicRK in sustaining cell wall integrity. One reason for diminished cell viability of the SmuvicK mutant is likely due to VicK's central role in maintaining cell wall integrity by modulating cellular murein hydrolase activity.…”

Section: Resultsmentioning

confidence: 99%

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Regulation of Bacteriocin Production and Cell Death by the VicRK Signaling System in Streptococcus mutans

et al. 2012

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The VicRK two-component signaling system modulates biofilm formation, genetic competence, and stress tolerance in Streptococcus mutans. We show here that the VicRK modulates bacteriocin production and cell viability, in part by direct modulation of competence-stimulating peptide (CSP) production in S. mutans. Global transcriptome and real-time transcriptional analysis of the VicK-deficient mutant (SmuvicK) revealed significant modulation of several bacteriocin-related loci, including nlmAB, nlmC, and nlmD (P < 0.001), suggesting a role for the VicRK in producing mutacins IV, V, and VI. Bacteriocin overlay assays revealed an altered ability of the vic mutants to kill related species. Since a well-conserved VicR binding site (TGTWAH-N 5 -TGTWAH) was identified within the comC coding region, we confirmed VicR binding to this sequence using DNA footprinting. Overexpression of the vic operon caused growth-phase-dependent repression of comC, comDE, and comX. In the vic mutants, transcription of nlmC/cipB encoding mutacin V, previously linked to CSP-dependent cell lysis, as well as expression of its putative immunity factor encoded by immB, were significantly affected relative to the wild type (P < 0.05). In contrast to previous reports that proposed a hyper-resistant phenotype for the VicK mutant in cell viability, the release of extracellular genomic DNA was significantly enhanced in SmuvicK (P < 0.05), likely as a result of increased autolysis compared with the parent. The drastic influence of VicRK on cell viability was also demonstrated using vic mutant biofilms. Taken together, we have identified a novel regulatory link between the VicRK and ComDE systems to modulate bacteriocin production and cell viability of S. mutans.

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Section: Resultsmentioning

confidence: 99%

“…The vicK and vicR genes of S. mutans encode an HK and RR, respectively, and regulate genetic transformation, biofilm formation, and stress tolerance (8,10,46,47,48,52). An unusual feature of VicRK, which is highly conserved in low GϩC Gram-positive bacteria, is that it is essential for viability in most bacteria (9).…”

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confidence: 99%

Regulation of Bacteriocin Production and Cell Death by the VicRK Signaling System in Streptococcus mutans

et al. 2012

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“…Chromosomal DNA of S. mutans was isolated according to the method of Hanna et al (18) and used as a template for PCR. To delete the pgdA (SMU.623c) gene in S. mutans UA159, we used a precise deletion method (13,26). A crossover PCR deletion product was constructed in two steps.…”

Section: Methodsmentioning

confidence: 99%

Streptococcus mutans SMU.623c Codes for a Functional, Metal-Dependent Polysaccharide Deacetylase That Modulates Interactions with Salivary Agglutinin

et al. 2009

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The genome sequence of the oral pathogen Streptococcus mutans predicts the presence of two putative polysaccharide deacetylases. The first, designated PgdA in this paper, shows homology to the catalytic domains of peptidoglycan deacetylases from Streptococcus pneumoniae and Listeria monocytogenes, which are both thought to be involved in the bacterial defense mechanism against human mucosal lysozyme and are part of the CAZY family 4 carbohydrate esterases. S. mutans cells in which the pgdA gene was deleted displayed a different colony texture and a slightly increased cell surface hydrophobicity and yet did not become hypersensitive to lysozyme as shown previously for S. pneumoniae. To understand this apparent lack of activity, the high-resolution X-ray structure of S. mutans PgdA was determined; it showed the typical carbohydrate esterase 4 fold, with metal bound in a His-His-Asp triad. Analysis of the protein surface showed that an extended groove lined with aromatic residues is orientated toward the active-site residues. The protein exhibited metaldependent de-N-acetylase activity toward a hexamer of N-acetylglucosamine. No activity was observed toward shorter chitooligosaccharides or a synthetic peptidoglycan tetrasaccharide. In agreement with the lysozyme data this would suggest that S. mutans PgdA does not act on peptidoglycan but on an as-yet-unidentified polysaccharide within the bacterial cell surface. Strikingly, the pgdA-knockout strain showed a significant increase in aggregation/agglutination by salivary agglutinin, in agreement with this gene acting as a deacetylase of a cell surface glycan.

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“…VicRK, a two-component system, is downregulated upon sprV inactivation and is involved in the regulation of glucosyl transferases and glucan-binding proteins that are instrumental for sucrose-dependent biofilm formation (25). Moreover, the VicRK system is also reported to be involved in tolerance to oxidative stress and the development of genetic competence (28). The CiaHR twocomponent system, which is upregulated upon sprV deletion, has been shown to be involved in biofilm formation, acid tolerance, genetic competence, and the expression of the stress-responsive protease HtrA (29).…”

Section: Figmentioning

confidence: 99%

Pleiotropic Regulation of Virulence Genes in Streptococcus mutans by the Conserved Small Protein SprV

2017

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Streptococcus mutans, an oral pathogen associated with dental caries, colonizes tooth surfaces as polymicrobial biofilms known as dental plaque. S. mutans expresses several virulence factors that allow the organism to tolerate environmental fluctuations and compete with other microorganisms. We recently identified a small hypothetical protein (90 amino acids) essential for the normal growth of the bacterium. Inactivation of the gene, SMU.2137, encoding this protein caused a significant growth defect and loss of various virulence-associated functions. An S. mutans strain lacking this gene was more sensitive to acid, temperature, osmotic, oxidative, and DNA damage-inducing stresses. In addition, we observed an altered protein profile and defects in biofilm formation, bacteriocin production, and natural competence development, possibly due to the fitness defect associated with SMU.2137 deletion. Transcriptome sequencing revealed that nearly 20% of the S. mutans genes were differentially expressed upon SMU.2137 deletion, thereby suggesting a pleiotropic effect. Therefore, we have renamed this hitherto uncharacterized gene as sprV (streptococcal pleiotropic regulator of virulence). The transcript levels of several relevant genes in the sprV mutant corroborated the phenotypes observed upon sprV deletion. Owing to its highly conserved nature, inactivation of the sprV ortholog in Streptococcus gordonii also resulted in poor growth and defective UV tolerance and competence development as in the case of S. mutans. Our experiments suggest that SprV is functionally distinct from its homologs identified by structure and sequence homology. Nonetheless, our current work is aimed at understanding the importance of SprV in the S. mutans biology.IMPORTANCE Streptococcus mutans employs several virulence factors and stress resistance mechanisms to colonize tooth surfaces and cause dental caries. Bacterial pathogenesis is generally controlled by regulators of fitness that are critical for successful disease establishment. Sometimes these regulators, which are potential targets for antimicrobials, are lost in the genomic context due to the lack of annotated homologs. This work outlines the regulatory impact of a small, highly conserved hypothetical protein, SprV, encoded by S. mutans. We show that SprV affects the transcript levels of various virulence factors required for normal growth, biofilm formation, stress tolerance, genetic competence, and bacteriocin production.KEYWORDS pleiotropic regulator, Streptococcus mutans, bacteriocins, biofilms, global virulence, stress response S treptococcus mutans expresses various stress tolerance mechanisms and virulence factors, which allow the organism to endure the detrimental oral environment, colonize tooth surfaces as dental plaque, and eventually cause caries by demineralization of the enamel (1). The coordinated expression of stress responsive and virulencerelated genes is critical for the persistence of S. mutans in the oral environment that

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The VicRK System of Streptococcus mutans Responds to Oxidative Stress

Cited by 73 publications

References 25 publications

Regulation of Bacteriocin Production and Cell Death by the VicRK Signaling System in Streptococcus mutans

Regulation of Bacteriocin Production and Cell Death by the VicRK Signaling System in Streptococcus mutans

Streptococcus mutans SMU.623c Codes for a Functional, Metal-Dependent Polysaccharide Deacetylase That Modulates Interactions with Salivary Agglutinin

Pleiotropic Regulation of Virulence Genes in Streptococcus mutans by the Conserved Small Protein SprV

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