Identification of
            <i>nlmTE</i>
            , the Locus Encoding the ABC Transport System Required for Export of Nonlantibiotic Mutacins in
            <i>Streptococcus mutans</i>

Hale, John K.; Heng, Nicholas C. K.; Jack, Ralph W.; Tagg, John

doi:10.1128/jb.187.14.5036-5039.2005

Cited by 52 publications

(54 citation statements)

References 28 publications

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“…Mutacin IV is a two-component bacteriocin that is composed of the NlmA and NlmB peptides, which are encoded by two transcriptionally linked genes (50). The dramatic decrease in the level of mutacin IV produced by the liaS mutant could be due to several factors including a reduction in the transcription of nlmA and nlmB or a deficiency in the export of the NlmA and NlmB peptides by the ABC transporter encoded by nlmT (17); therefore, the levels of transcription of nlmA and nlmT were measured in strains UA159, IBS148, and IBS148/pIB55. As shown in Fig.…”

Section: Vol 76 2008 Lias and Virulence In S Mutans 3095mentioning

confidence: 99%

“…S. mutans has the capacity to produce mutacin, a bacteriocin, to suppress the growth of other competitor bacteria present in the dental plaque community (12,19,36,38). In particular, S. mutans strain UA159 produces a mutacin that is active against sanguinis group and mitis group streptococci, the main competitors of S. mutans in the oral cavity (17,18,50). It was previously shown that both gbpC expression and mutacin production are modulated by the same regulatory network controlled by LuxS (35).…”

Section: Vol 76 2008 Lias and Virulence In S Mutans 3095mentioning

confidence: 99%

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LiaS Regulates Virulence Factor Expression in Streptococcus mutans

Chong

Drake²,

Biswas³

2008

Infect Immun

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Streptococcus mutans, a major oral pathogen responsible for dental caries formation, possesses a variety of mechanisms for survival in the human oral cavity, where the conditions of the external environment are diverse and in a constant state of flux. The formation of biofilms, survival under conditions of acidic pH, and production of mutacins are considered to be important virulence determinants displayed by this organism. Biofilm formation is facilitated by the production of GbpC, an important cell surface-associated protein that binds to glucan, an adhesive polysaccharide produced by the organism itself. To better understand the nature of the environmental cues that induce GbpC production, we examined the roles of 14 sensor kinases in the expression of gbpC in S. mutans strain UA159. We found that only the LiaS sensor kinase regulates gbpC expression, while the other sensor kinases had little or no effect on gbpC expression. We also found that while LiaS negatively regulates gbpC expression, the inactivation of its cognate response regulator, LiaR, does not appear to affect the expression of gbpC. Since both gbpC expression and mutacin IV production are regulated by a common regulatory network, we also tested the effect of the liaS mutation on mutacin production and found that LiaS positively regulates mutacin IV production. Furthermore, reverse transcription-PCR analysis suggests that LiaS does so by regulating the expression of nlmA, which encodes a peptide component of mutacin IV, and nlmT, which encodes an ABC transporter. As with the expression of gbpC, LiaR did not have any apparent effect on mutacin IV production. Based on the results of our study, we speculate that LiaS is engaged in cross talk with one or more response regulators belonging to the same family as LiaR, enabling LiaS to regulate the expression of several genes coding for virulence factors.

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Section: Vol 76 2008 Lias and Virulence In S Mutans 3095mentioning

confidence: 99%

Section: Vol 76 2008 Lias and Virulence In S Mutans 3095mentioning

confidence: 99%

LiaS Regulates Virulence Factor Expression in Streptococcus mutans

Chong

Drake²,

Biswas³

2008

Infect Immun

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“…Together, the com-controlled NlmC/ImmB (also known as CipB/ CipI) pathway was shown to effect cellular autolysis and extracellular genomic DNA (eDNA) release (37), which contributes to the structural and functional integrity of the S. mutans' biofilm (19,36,37). Involvement of ComDE in regulating the transcription and/or production of mutacins I, IV, V, and VI has also been demonstrated by several labs (12,13,15,19,21,28,37,55,57,58). The antimicrobial spectrum of mutacin IV is specifically against members of the mitis group of oral streptococci, while those of mutacins I, II, and III are broader (38)(39)(40).…”

mentioning

confidence: 99%

“…Based on a survey of 143 strains of S. mutans used to assess bacteriocin production in vitro, 98 strains were reported to produce at least one bacteriocin (44). One of the major pathways of S. mutans for regulating bacteriocin production is via the ComDE two-component signal transduction system (TCSTS) that responds to accumulation of the competence stimulating peptide (CSP) whose precursor peptide is encoded by comC (12,21,28,37,55,58). The ComDE is 1 of 13 TCSTSs in S. mutans (3,24) that help respond to environmental stimuli by transmitting signals from a membrane-bound histidine kinase (HK) to an intracellular response regulator (RR) protein via transphosphorylation, which in turn, regulates the transcription of its target genes (49).…”

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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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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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“…However, inhibitory activity was restored only to the comC mutant (Table 2), implicating the ABC transporter complex ComAB in streptocin export. ComAB secretes mature CSP following cleavage of the precursor peptide ComC at a specific Gly-Gly motif (10), and ComAB-like transporters (e.g., NlmTE in Streptococcus mutans [4]) are common exit portals for nonmodified (i.e., class II) Gly-Gly-containing peptide bacteriocins (3,5). Furthermore, a BLAST (1) search of the S. gordonii Challis genome sequence did not reveal an alternative ABC transport system.…”

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confidence: 99%

Competence-Dependent Bacteriocin Production by Streptococcus gordonii DL1 (Challis)

Heng

Tagg

Tompkins³

2007

J Bacteriol

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The production of streptocins STH 1 and STH 2 by Streptococcus gordonii DL1 (Challis) is directly controlled by the competence regulon, which requires intact comR and comAB loci. The streptocin (sth) locus comprises two functional genes, sthA and sthB. Whereas STH 1 activity requires sthA alone, STH 2 activity depends on both genes.In the 1970s, reported the production of streptocin STH 1 , a proteinaceous antimicrobial agent (bacteriocin), by the naturally transformable Streptococcus gordonii (formerly Streptococcus sanguis) strain Challis (also known as DL1 and NCTC 7868). Streptocin STH 1 biosynthesis coincided with the development of competence for genetic transformation (20, 21), a relationship supported by later studies (8,23). The inhibitory spectrum of streptocin STH 1 was initially reported to include other S. gordonii strains (e.g., strains Wicky and C219) and select strains of Streptococcus mitis and Streptococcus oralis (8,23). However, we have observed that the bacteriocin activity targeting S. mitis and S. oralis appears to be linked to the beta-hemolytic phenotype of strain Challis because S. gordonii OB164 (originally designated DL1-Challis), a non-beta-hemolytic strain indistinguishable from DL1 biochemically (API 20 Strep; bioMérieux, France) and genotypically (18), exhibited inhibitory activity only against S. gordonii isolates. This suggested that strain DL1 produces two bacteriocins: the previously described STH 1 (20) and the newly designated STH 2 , a bacteriocin that targets certain non-S. gordonii strains and is associated with the beta-hemolytic phenotype. Based on our speculation that genetic competence and bacteriocin production may be functionally related in strain DL1 (23), the aims of the present study were to determine whether bacteriocin biosynthesis is genetically associated with competence development and to define the locus encoding the inhibitory/hemolytic agents.(Parts of this work were presented at the 7th ASM Conference on Streptococcal Genetics, Saint Malo, France [7a].)Association of competence and bacteriocin/␤-hemolysin production. Competence development in S. gordonii is analogous to competence development in Streptococcus pneumoniae, occurring in two distinct stages, early and late (10, 13). The early stage involves a quorum-sensing signal transduction circuit comprising a secreted competence-stimulating peptide (CSP), its cell surface receptor ComD (a histidine kinase), and ComE, the primary transcriptional regulator of competence (10, 13). ComE, when activated by ComD, upregulates the comCDE (signal transduction), comAB (CSP secretion), and comX operons (13). ComX, an alternative sigma factor, connects the early and late stages by activating expression of the late competence operons that are responsible for DNA uptake and processing (17). Several key components of the S. gordonii competence regulon have been identified, including comCDE, comAB, comYA (DNA uptake), and duplicate comR (comX homologue) loci (6,7,15,16).In this study, early (comC, comE, comA, comB, an...

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Identification of nlmTE , the Locus Encoding the ABC Transport System Required for Export of Nonlantibiotic Mutacins in Streptococcus mutans

Cited by 52 publications

References 28 publications

LiaS Regulates Virulence Factor Expression in Streptococcus mutans

LiaS Regulates Virulence Factor Expression in Streptococcus mutans

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

Competence-Dependent Bacteriocin Production by Streptococcus gordonii DL1 (Challis)

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