A novel function for the competence inducing peptide, XIP, as a cell death effector of<i>Streptococcus mutans</i>

Wenderska, Iwona B.; Lukenda, Nikola; Cordova, Martha; Magarvey, Nathan A.; Cvitkovitch, Dennis G.; Senadheera, Dilani B.

doi:10.1111/j.1574-6968.2012.02660.x

Cited by 46 publications

(80 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A role for XIP in growth inhibition and cell death has been reported recently (23,26). Given that the induction of comX or comS by sXIP was most pronounced in early-exponential-phase cells, we tested whether the growth of S. mutans was affected by high concentrations of XIP if sXIP was added after cells had exited early-exponential phase.…”

Section: Resultsmentioning

confidence: 99%

“…It has also been proposed that at least some of the regulators that influence transformation efficiency in S. mutans, such as HtrA, HdrRM, BsrRM, CiaHR, and ComDE, exert their effects on competence via the ComRS system through as yet undefined mechanisms (20). It is also not well understood how the ComRS and ComDE systems overlap to regulate competence gene expression or how the addition of XIP or CSP at high concentrations induces growth inhibition or cell death (23,24). Also of note, it was shown recently that the ability of the ComRS system to activate comX can be affected by a third peptide that influences competence through the TCS ScnRK (25).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Growth Phase and pH Influence Peptide Signaling for Competence Development in Streptococcus mutans

Guo

Ahn

Kaspar

et al. 2013

Journal of Bacteriology

View full text Add to dashboard Cite

The development of competence by the dental caries pathogen Streptococcus mutans is mediated primarily through the alternative sigma factor ComX (SigX), which is under the control of multiple regulatory systems and activates the expression of genes involved in DNA uptake and recombination. Here we report that the induction of competence and competence gene expression by XIP (sigX-inducing peptide) and CSP (competence-stimulating peptide) is dependent on the growth phase and that environmental pH has a potent effect on the responses to XIP. A dramatic decline in comX and comS expression was observed in midand late-exponential-phase cells. XIP-mediated competence development and responses to XIP were optimal around a neutral pH, although mid-exponential-phase cells remained refractory to XIP treatment, and acidified late-exponential-phase cultures were resistant to killing by high concentrations of XIP. Changes in the expression of the genes for the oligopeptide permease (opp), which appears to be responsible for the internalization of XIP, could not entirely account for the behaviors observed. Interestingly, comS and comX expression was highly induced in response to endogenously overproduced XIP or ComS in mid-exponential-phase cells. In contrast to the effects of pH on XIP, competence induction and responses to CSP in complex medium were not affected by pH, although a decreased response to CSP in cells that had exited early-exponential phase was observed. Collectively, these results indicate that competence development may be highly sensitive to microenvironments within oral biofilms and that XIP and CSP signaling in biofilms could be spatially and temporally heterogeneous.

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Growth Phase and pH Influence Peptide Signaling for Competence Development in Streptococcus mutans

Guo

Ahn

Kaspar

et al. 2013

Journal of Bacteriology

View full text Add to dashboard Cite

show abstract

“…Depending on the conditions, XIP activation of ComX occurs uniformly throughout the population, whereas CSP activates comX in only a subpopulation of cells (9,14). Of note, physiologically high levels of XIP or CSP can also induce cell death (10,(13)(14)(15), some of which occurs as a result of the presence of endogenously produced bacteriocins or autolytic enzymes (15)(16)(17)(18). Evidence is accumulating that there are multiple other control points modulating competence, transformation efficiency, and XIP-or CSP-mediated cell death in S. mutans, including, but not limited to, CiaRH, HtrA, IrvRA, and HdrRM (5,8,15,(19)(20)(21)(22).…”

mentioning

confidence: 99%

“…Importantly, the mechanisms governing comX gene expression, as well as the amount and activity of ComX in cells, differ substantially between species. Thus, dissecting how comX expression and ComX activity are regulated is central to understanding how the decision to commit to competence is determined and how virulence traits of S. mutans, such as biofilm formation and acid tolerance, are integrated with the competence regulatory system (5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

Discovery of Novel Peptides Regulating Competence Development in Streptococcus mutans

et al. 2014

View full text Add to dashboard Cite

A MarR-like transcriptional repressor (RcrR) and two predicted ABC efflux pumps (RcrPQ) encoded by a single operon were recently shown to be dominant regulators of stress tolerance and development of genetic competence in the oral pathogen Streptococcus mutans. Here, we focused on polar (⌬rcrR-P) and nonpolar (⌬rcrR-NP) rcrR mutants, which are hyper-and nontransformable, respectively, to dissect the mechanisms by which these mutations impact competence. We discovered two open reading frames (ORFs) in the 3= end of the rcrQ gene that encode peptides of 27 and 42 amino acids (aa) which are also dramatically upregulated in the ⌬rcrR-NP strain. Deletion of, or start codon mutations in, the ORFs for the peptides in the ⌬rcrR-NP background restored competence and sensitivity to competence-stimulating peptide (CSP) to levels seen in the ⌬rcrR-P strain. Overexpression of the peptides adversely affected competence development. Importantly, overexpression of mutant derivatives of the ABC exporters that lacked the peptides also resulted in impaired competence. FLAG-tagged versions of the peptides could be detected in S. mutans, and FLAG tagging of the peptides impaired their function. The competence phenotypes associated with the various mutations, and with overexpression of the peptides and ABC transporters, were correlated with the levels of ComX protein in cells. Collectively, these studies revealed multiple novel mechanisms for regulation of competence development by the components of the rcrRPQ operon. Given their intimate role in competence and stress tolerance, the rcrRPQ-encoded peptides may prove to be useful targets for therapeutics to diminish the virulence of S. mutans.

show abstract

“…Earlier reports have also demonstrated that the increase in the concentration (2-4 lM) of CSP mediated cell-killing and growth arrest of S. mutans [39,40]. Likewise, the S. mutans on exposure to 10 lM of synthetic XIP (sXIP) has shown the killing effect, naturally score the phenomena of exploiting the pheromones (XIP) as a potent effector molecules to treat dental caries [41].…”

Section: S Mutans and Dental Cariesmentioning

confidence: 99%

Plausible Drug Targets in the Streptococcus mutans Quorum Sensing Pathways to Combat Dental Biofilms and Associated Risks

2015

View full text Add to dashboard Cite

Streptococcus mutans, a Gram positive facultative anaerobe, is one among the approximately seven hundred bacterial species to exist in human buccal cavity and cause dental caries. Quorum sensing (QS) is a celldensity dependent communication process that respond to the inter/intra-species signals and elicit responses to show behavioral changes in the bacteria to an aggressive forms. In accordance to this phenomenon, the S. mutans also harbors a Competing Stimulating Peptide (CSP)-mediated quorum sensing, ComCDE (Two-component regulatory system) to regulate several virulence-associated traits that includes the formation of the oral biofilm (dental plaque), genetic competence and acidogenicity. The QS-mediated response of S. mutans adherence on tooth surface (dental plaque) imparts antibiotic resistance to the bacterium and further progresses to lead a chronic state, known as periodontitis. In recent years, the oral streptococci, S. mutans are not only recognized for its cariogenic potential but also well known to worsen the infective endocarditis due to its inherent ability to colonize and form biofilm on heart valves. The review significantly appreciate the increasing complexity of the CSP-mediated quorum-sensing pathway with a special emphasis to identify the plausible drug targets within the system for the development of anti-quorum drugs to control biofilm formation and associated risks.

show abstract

A novel function for the competence inducing peptide, XIP, as a cell death effector ofStreptococcus mutans

Cited by 46 publications

References 23 publications

Growth Phase and pH Influence Peptide Signaling for Competence Development in Streptococcus mutans

Growth Phase and pH Influence Peptide Signaling for Competence Development in Streptococcus mutans

Discovery of Novel Peptides Regulating Competence Development in Streptococcus mutans

Plausible Drug Targets in the Streptococcus mutans Quorum Sensing Pathways to Combat Dental Biofilms and Associated Risks

Contact Info

Product

Resources

About