Involvement of Sensor Kinases in the Stress Tolerance Response of<i>Streptococcus mutans</i>

Biswas, Indranil; Drake, Laura; Erkina, Dasha; Biswas, Saswati

doi:10.1128/jb.00990-07

Cited by 101 publications

(127 citation statements)

References 68 publications

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“…These results suggest that inactivation of each of these systems results in a mutant that has a reduced growth rate at acidic pH. Recent studies have shown that several TCS have been involved in acid resistance in S. mutans (Ahn et al, 2006;Biswas et al, 2008;Li et al, 2002;Lévesque et al, 2007;Kawada-Matsuo et al, 2009). Some of the TCS identified to be involved in acid tolerance in these studies appear to be different from those in our study, probably owing to the differences in the strains, mutant construction, growth conditions and assay methods.…”

Section: Effect Of Inactivation Of the Histidine Kinases (Hk) On Atrmentioning

confidence: 76%

“…Using real-time qRT-PCR, we confirmed the same trend in the expression of these genes, including the genes encoding their cognate response regulators, in response to acidic pH (Table 2). In the S. mutans genome, there are 14 TCSs, and at least one orphan response regulator has been identified (Ajdic et al, 2002;Biswas et al, 2008;Idone et al, 2003). Some of these systems, such as LiaSR (formerly HK/ RR11), CiaHR, ComDE and CovR, have been found to play a role in acid resistance and considered as a major attribute to the virulence of S. mutans (Ahn et al, 2006;Idone et al, 2003;Li et al, 2001bLi et al, , 2002Lévesque et al, 2007;Kawada-Matsuo et al, 2009).…”

Section: Upregulated Genesmentioning

confidence: 99%

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Global transcriptional analysis of acid-inducible genes in Streptococcus mutans: multiple two-component systems involved in acid adaptation

et al. 2009

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Streptococcus mutans in dental biofilms is regularly exposed to cycles of acidic pH during the ingestion of fermentable dietary carbohydrates. The ability of S. mutans to tolerate low pH is crucial for its virulence and pathogenesis in dental caries. To better understand its acid tolerance mechanisms, we performed genome-wide transcriptional analysis of S. mutans in response to an acidic pH signal. The preliminary results showed that adaptation of S. mutans to pH 5.5 induced differential expression of nearly 14 % of the genes in the genome, including 169 upregulated genes and 108 downregulated genes, largely categorized into nine functional groups. One of the most interesting findings was that the genes encoding multiple two-component systems (TCSs), including CiaHR, LevSR, LiaSR, ScnKR, Hk/Rr1037/1038 and ComDE, were upregulated during acid adaptation. Real-time qRT-PCR confirmed the same trend in the expression profiles of these genes at pH 5.5. To determine the roles of these transduction systems in acid adaptation, mutants with a deletion of the histidine-kinase-encoding genes were constructed and assayed for the acid tolerance response (ATR). The results revealed that inactivation of each of these systems resulted in a mutant that was impaired in ATR, since pre-exposure of these mutants to pH 5.5 did not induce the same level of protection against lethal pH levels as the parent did. A competitive fitness assay showed that all the mutants were unable to compete with the parent strain for persistence in dual-strain mixed cultures at acidic pH, although, with the exception of the mutant in liaS, little effect was observed at neutral pH. The evidence from this study suggests that the multiple TCSs are required for S. mutans to orchestrate its signal transduction networks for optimal adaptation to acidic pH.

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Section: Effect Of Inactivation Of the Histidine Kinases (Hk) On Atrmentioning

confidence: 76%

Section: Upregulated Genesmentioning

confidence: 99%

Global transcriptional analysis of acid-inducible genes in Streptococcus mutans: multiple two-component systems involved in acid adaptation

et al. 2009

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“…Gryllos et al (21,22) reported that the presence of Mg 2ϩ in the growth medium stimulated the activity of CovR/S, specifically acting as a stimulant for CovS. In the absence of CovS, it is possible that Mg 2ϩ activates one of the previously identified TCS of S. mutans (5), which subsequently leads to the transcription of covR or the activation of CovR in S. mutans. However, the increase in the expression of covR under in vitro conditions was observed using concentrations of Mg 2ϩ that are significantly higher than physiological conditions; the concentration of Mg 2ϩ in saliva is 0.22 mM, while the concentration of Mg 2ϩ in blood is approximately 1 mM (22,47).…”

Section: Discussionmentioning

confidence: 99%

Modulation ofcovRExpression inStreptococcus mutansUA159

2008

Self Cite

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The biofilm-forming Streptococcus mutans is a gram-positive bacterium that resides in the human oral cavity and is considered to be the primary etiological agent in the formation of dental caries. The global response regulator CovR, which lacks a cognate sensor kinase, is essential for the pathogenesis and biofilm formation of this bacterium, but it is not clear how covR expression is regulated in S. mutans. In this communication, we present the results of our studies examining various factors that regulate the expression of covR in S. mutans UA159. The results of Southern hybridization and PCR analysis indicated that CovR is an orphan response regulator in various isolates of S. mutans. The transcriptional start site for covR was found to be 221 base pairs upstream of the ATG start codon, and site-directed mutagenesis of the upstream TATAAT box confirmed our findings. The expression of covR is growth phase dependent, with maximal expression observed during exponential-growth phase. While changes to the growth temperature did not significantly affect the expression of covR, increasing the pH or the concentration of Mg 2؉ in the growth medium leads to an increase in covR expression. The results of semiquantitative reverse transcriptase PCR analysis and in vivo transcriptionalfusion reporter assays indicated that CovR autoregulates its own expression; this was verified by the results of electrophoretic mobility shift assays and DNase I protection assays, which demonstrated direct binding of CovR to the promoter region. Apparently, regulation by Mg 2؉ and the autoregulation of covR are not linked. A detailed analysis of the regulation of CovR may lead to a better understanding of the pathogenesis of S. mutans, as well as providing further insight into the prevention of dental caries.

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“…S. mutans adheres to the tooth surface and forms dental plaque, a classic biofilm. The pH of the oral cavity is predominantly acidic; within the dental plaque, S. mutans induces an acid-tolerance response that favors its survival under low pH conditions (4).…”

Section: Introductionmentioning

confidence: 99%

Toluene permeabilization differentially affects F- and P-type ATPase activities present in the plasma membrane of Streptococcus mutans

Thedei

Leitão

Bolean

et al. 2008

Braz J Med Biol Res

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Streptococcus mutans membrane-bound P-and F-type ATPases are responsible for H + extrusion from the cytoplasm thus keeping intracellular pH appropriate for cell metabolism. Toluene-permeabilized bacterial cells have long been used to study total membrane-bound ATPase activity, and to compare the properties of ATPase in situ with those in membrane-rich fractions. The aim of the present research was to determine if toluene permeabilization can significantly modify the activity of membranebound ATPase of both F-type and P-type. ATPase activity was assayed discontinuously by measuring phosphate release from ATP as substrate. Treatment of S. mutans membrane fractions with toluene reduced total ATPase activity by approximately 80% and did not allow differentiation between F-and P-type ATPase activities by use of the standard inhibitors vanadate (3 µM) and oligomycin (4 µg/mL). Transmission electron microscopy shows that, after S. mutans cells permeabilization with toluene, bacterial cell wall and plasma membrane are severely injured, causing cytoplasmic leakage. As a consequence, loss of cell viability and disruption of H + extrusion were observed. These data suggest that treatment of S. mutans with toluene is an efficient method for cell disruption, but care should be taken in the interpretation of ATPase activity when toluene-permeabilized cells are used, because results may not reflect the real P-and F-type ATPase activities present in intact cell membranes. The mild conditions used for the preparation of membrane fractions may be more suitable to study specific ATPase activity in the presence of biological agents, since this method preserves ATPase selectivity for standard inhibitors.

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Involvement of Sensor Kinases in the Stress Tolerance Response ofStreptococcus mutans

Cited by 101 publications

References 68 publications

Global transcriptional analysis of acid-inducible genes in Streptococcus mutans: multiple two-component systems involved in acid adaptation

Global transcriptional analysis of acid-inducible genes in Streptococcus mutans: multiple two-component systems involved in acid adaptation

Modulation ofcovRExpression inStreptococcus mutansUA159

Toluene permeabilization differentially affects F- and P-type ATPase activities present in the plasma membrane of Streptococcus mutans

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