The Streptococcus mutans Cid and Lrg systems modulate virulence traits in response to multiple environmental signals

Ahn, Sang Joon; Rice, Kelly C.; Oleas, Janneth; Bayles, Kenneth W.; Burne, Robert A.

doi:10.1099/mic.0.039586-0

Cited by 64 publications

(209 citation statements)

References 55 publications

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“…Ahn et al previously showed that mutagenesis of VicK affected maturation of AtlA (2). Using planktonic culture-based autolysis assays, these authors showed that a VicK-deficient mutant was hyper-resistant to autolysis (2). Using our SmuvicK mutant and its UA159 parent, we successfully validated these results via autolysis assays (data not shown).…”

Section: Resultsmentioning

confidence: 51%

“…Emerging reports from VicKR homologs in other bacteria suggest that one of its primary functions is in the maintenance of cell wall metabolism (5, 9). Ahn et al previously showed that mutagenesis of VicK affected maturation of AtlA (2). Using planktonic culture-based autolysis assays, these authors showed that a VicK-deficient mutant was hyper-resistant to autolysis (2).…”

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: 51%

Section: Resultsmentioning

confidence: 99%

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

et al. 2012

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“…Since the process of CSP-induced death leads to cell lysis, we searched the genome of S. mutans UA159 reference strain for lysis effectors. We found two functional murein hydrolases, SMU.609 (33) and AtlA (34,35), two putative membrane proteins similar to bacteriophages holin proteins, LrgB and CidB (36), and six additional putative autolysins (SMU.22, SMU.76, SMU.704, SMU.707, SMU.772, and SMU.836) ( Table 2). In order to determine if one or more of these proteins were responsible for the CSP-induced cell lysis phenotype, S. mutans isogenic mutants defective in SMU.574 (LrgB), SMU.609, SMU.689 (AtlA), SMU.704, SMU.772, SMU.836, and SMU.1700 (CidB) were generated, and their growth kinetics were analyzed in the presence of sCSP.…”

Section: Resultsmentioning

confidence: 98%

Cell Death of Streptococcus mutans Induced by a Quorum-Sensing Peptide Occurs via a Conserved Streptococcal Autolysin

Dufour

Lévesque

2013

J Bacteriol

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Streptococcus mutans, a member of the human indigenous oral microbiome, produces a quorum-sensing peptide called the competence-stimulating peptide (CSP) pheromone. We previously demonstrated that S. mutans expresses its CSP pheromone under specific stresses and responds to high levels of CSP by inducing cell death in a fraction of the bacterial population. Streptococci lack the classical SOS response, and the induction of the SigX regulon has been proposed to act as a general stress response in Gram-positive bacteria. We show here that inactivation of SigX abolished the CSP-induced cell death phenotype. Among SigXregulated genes, SMU.836 (now named lytF Sm ), encoding a conserved streptococcal protein, is a functional peptidoglycan hydrolase involved in CSP-induced cell lysis. We also demonstrated that LytF Sm is most likely a self-acting autolysin, since LytF Sm produced by attacker cells cannot trigger CSP-induced lysis of LytF Sm -deficient target cells present in the same environment. Electron microscopy revealed important morphological changes accompanying autolysis of CSP-induced wild-type cultures that were absent in the LytF Sm -deficient mutant. The LytF Sm promoter was activated in the physiological context of elevated concentrations of the CSP pheromone under stress conditions, such as exposure to heat, hydrogen peroxide, and acid. In a long-term survival assay, the viability of a mutant deficient in LytF Sm autolysin was significantly lower than that observed for the wild-type strain. The results of this study suggest that cell death of S. mutans induced by its quorum-sensing CSP pheromone may represent a kind of altruistic act that provides a way for the species to survive environmental stresses at the expense of some of its cells.

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“…Holin-like proteins in the dental plaque-forming Firmicutes member Streptococcus mutans have been shown to affect both biofilm formation and oxidative stress responses (66). These proteins, CidA (TC no.…”

Section: Involvement Of Holins In Bacterial Biofilm Formationmentioning

confidence: 99%

“…Phage lytic systems can reduce biofilm formation in some instances (100), while conversely, biofilms may exhibit differential resistance to the lytic activities of phage (101). Holins also play roles in stress responses (102), virulence (66), release of toxins and other proteins (103,104), and bacterial sporulation and spore germination (105). They may play widespread roles in protein trafficking and secretion to the extracellular environment (18).…”

Section: Perspectives and Conclusion: A Plethora Of Holin Functions mentioning

confidence: 99%

Holins in Bacteria, Eukaryotes, and Archaea: Multifunctional Xenologues with Potential Biotechnological and Biomedical Applications

Saier

Reddy

2015

J Bacteriol

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bHolins form pores in the cytoplasmic membranes of bacteria for the primary purpose of releasing endolysins that hydrolyze the cell wall and induce cell death. Holins are encoded within bacteriophage genomes, where they promote cell lysis for virion release, and within bacterial genomes, where they serve a diversity of potential or established functions. These include (i) release of gene transfer agents, (ii) facilitation of programs of differentiation such as those that allow sporulation and spore germination, (iii) contribution to biofilm formation, (iv) promotion of responses to stress conditions, and (v) release of toxins and other proteins. There are currently 58 recognized families of holins and putative holins with members exhibiting between 1 and 4 transmembrane ␣-helical spanners, but many more families have yet to be discovered. Programmed cell death in animals involves holin-like proteins such as Bax and Bak that may have evolved from bacterial holins. Holin homologues have also been identified in archaea, suggesting that these proteins are ubiquitous throughout the three domains of life. Phage-mediated cell lysis of dualmembrane Gram-negative bacteria also depends on outer membrane-disrupting "spanins" that function independently of, but in conjunction with, holins and endolysins. In this minireview, we provide an overview of their modes of action and the first comprehensive summary of the many currently recognized and postulated functions and uses of these cell lysis systems. It is anticipated that future studies will result in the elucidation of many more such functions and the development of additional applications.

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The Streptococcus mutans Cid and Lrg systems modulate virulence traits in response to multiple environmental signals

Cited by 64 publications

References 55 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

Cell Death of Streptococcus mutans Induced by a Quorum-Sensing Peptide Occurs via a Conserved Streptococcal Autolysin

Holins in Bacteria, Eukaryotes, and Archaea: Multifunctional Xenologues with Potential Biotechnological and Biomedical Applications

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