SloR modulation of the Streptococcus mutans acid tolerance response involves the GcrR response regulator as an essential intermediary

Dunning, Daniel W.; McCall, Lathan W.; Powell, William F.; Arscott, W. Tristram; McConocha, Erin M.; McClurg, Cheryl J.; Goodman, Steven D.; Spatafora, Grace A.

doi:10.1099/mic.0.2007/012492-0

Cited by 32 publications

(49 citation statements)

References 51 publications

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“…Despite our repeated attempts, we were not able to (13). Since several known ATR genes have shown to be positively regulated by GcrR, which include the F 1 F 0 -ATPase atpA/E and the bacterial signal recognition particle ffh (13), it is possible that expression of gcrR is upregulated in response to increased acid production resulting from glutamate metabolism. Another gene of interest that may have a regulatory effect on glnQHMP transcription is the marR homolog, Smu.124, which was downregulated 2.4-fold in response to the addition of glutamate (data not shown).…”

Section: Figmentioning

confidence: 92%

“…1A) (47). Despite our repeated attempts, we were not able to (13). Since several known ATR genes have shown to be positively regulated by GcrR, which include the F 1 F 0 -ATPase atpA/E and the bacterial signal recognition particle ffh (13), it is possible that expression of gcrR is upregulated in response to increased acid production resulting from glutamate metabolism.…”

Section: Figmentioning

confidence: 93%

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Characterization of a Glutamate Transporter Operon, glnQHMP , in Streptococcus mutans and Its Role in Acid Tolerance

et al. 2010

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Glutamate contributes to the acid tolerance response (ATR) of many Gram-negative and Gram-positive bacteria, but its role in the ATR of the oral bacterium Streptococcus mutans is unknown. This study describes the discovery and characterization of a glutamate transporter operon designated glnQHMP (Smu.1519 to Smu.1522) and investigates its potential role in acid tolerance. Deletion of glnQHMP resulted in a 95% reduction in transport of radiolabeled glutamate compared to the wild-type UA159 strain. The addition of glutamate to metabolizing UA159 cells resulted in an increased production of acidic end products, whereas the glnQHMP mutant produced less lactic acid than UA159, suggesting a link between glutamate metabolism and acid production and possible acid tolerance. To investigate this possibility, we conducted a microarray analysis with glutamate and under pH 5.5 and pH 7.5 conditions which showed that expression of the glnQHMP operon was downregulated by both glutamate and mild acid. We also measured the growth kinetics of UA159 and its glnQHMP-negative derivative at pH 5.5 and found that the mutant doubled at a much slower rate than the parent strain but survived at pH 3.5 significantly better than the wild type. Taken together, these findings support the involvement of the glutamate transporter operon glnQHMP in the acid tolerance response in S. mutans.

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Section: Figmentioning

confidence: 92%

Section: Figmentioning

confidence: 93%

Characterization of a Glutamate Transporter Operon, glnQHMP , in Streptococcus mutans and Its Role in Acid Tolerance

et al. 2010

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“…Their roles in acid adaptation are unclear. However, sloR is known to encode a metal-dependent transcriptional regulator involved in regulating the sloABCR operon for Mn and Fe uptake (Dunning et al, 2008). A recent study has linked the expression of the sloABCR operon to the acid stress response in S. mutans (Dunning et al, 2008;Idone et al, 2003).…”

Section: Upregulated Genesmentioning

confidence: 99%

“…However, sloR is known to encode a metal-dependent transcriptional regulator involved in regulating the sloABCR operon for Mn and Fe uptake (Dunning et al, 2008). A recent study has linked the expression of the sloABCR operon to the acid stress response in S. mutans (Dunning et al, 2008;Idone et al, 2003). It is also known that rgg encodes a transcriptional regulator in many Gram-positive bacteria, including S. mutans (Ajdic et al, 2002).…”

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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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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“…GcrR has also been shown to upregulate the expression of genes required for the acid tolerance response, which enables S. mutans to survive at pHs as low as 3.0. Rather than responding directly to acidic pHs, however, the transcription of gcrR is itself regulated by the transcriptional repressor SloR, whose repression is relieved under manganese-deprived and acidic conditions (141).…”

Section: Two-component Signal Transduction Systemsmentioning

confidence: 99%

StreptococcusAdherence and Colonization

Nobbs

Lamont

Jenkinson

2009

Microbiol Mol Biol Rev

552

569

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SUMMARY Streptococci readily colonize mucosal tissues in the nasopharynx; the respiratory, gastrointestinal, and genitourinary tracts; and the skin. Each ecological niche presents a series of challenges to successful colonization with which streptococci have to contend. Some species exist in equilibrium with their host, neither stimulating nor submitting to immune defenses mounted against them. Most are either opportunistic or true pathogens responsible for diseases such as pharyngitis, tooth decay, necrotizing fasciitis, infective endocarditis, and meningitis. Part of the success of streptococci as colonizers is attributable to the spectrum of proteins expressed on their surfaces. Adhesins enable interactions with salivary, serum, and extracellular matrix components; host cells; and other microbes. This is the essential first step to colonization, the development of complex communities, and possible invasion of host tissues. The majority of streptococcal adhesins are anchored to the cell wall via a C-terminal LPxTz motif. Other proteins may be surface anchored through N-terminal lipid modifications, while the mechanism of cell wall associations for others remains unclear. Collectively, these surface-bound proteins provide Streptococcus species with a “coat of many colors,” enabling multiple intimate contacts and interplays between the bacterial cell and the host. In vitro and in vivo studies have demonstrated direct roles for many streptococcal adhesins as colonization or virulence factors, making them attractive targets for therapeutic and preventive strategies against streptococcal infections. There is, therefore, much focus on applying increasingly advanced molecular techniques to determine the precise structures and functions of these proteins, and their regulatory pathways, so that more targeted approaches can be developed.

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SloR modulation of the Streptococcus mutans acid tolerance response involves the GcrR response regulator as an essential intermediary

Cited by 32 publications

References 51 publications

Characterization of a Glutamate Transporter Operon, glnQHMP , in Streptococcus mutans and Its Role in Acid Tolerance

Characterization of a Glutamate Transporter Operon, glnQHMP , in Streptococcus mutans and Its Role in Acid Tolerance

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

StreptococcusAdherence and Colonization

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