The Two-Component Regulatory System TCS08 Is Involved in Cellobiose Metabolism of<i>Streptococcus pneumoniae</i>R6

McKessar, Stuart J.; Hakenbeck, Regine

doi:10.1128/jb.01170-06

Cited by 54 publications

(82 citation statements)

References 46 publications

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“…Apparent homologues of Smu1452 have been found in Streptococcus pneumoniae R6 and Streptococcus gordonii, and in both cases, they are part of a well-conserved cellobiose operon (http://www .oralgen.lanl.gov/). Consistent with our finding, the homologue of Smu1452 in S. pneumoniae appears necessary for cellobiose utilization (20). We are currently exploring the potential role of this hypothetical protein in carbohydrate transport and catabolism by S. mutans.…”

Section: Discussionsupporting

confidence: 70%

Transcriptional Regulation of the Cellobiose Operon of Streptococcus mutans

2009

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The ability of Streptococcus mutans to catabolize cellobiose, a ␤-linked glucoside generated during the hydrolysis of cellulose, is shown to be regulated by a transcriptional regulator, CelR, which is encoded by an operon with a phospho-␤-glucosidase (CelA) and a cellobiose-specific sugar phosphotransferase system (PTS) permease (EII Cel ). The roles of CelR, EII Cel components, and certain fructose/mannose-PTS permeases in the transcriptional regulation of the cel locus were analyzed. The results revealed that (i) the celA and celB (EIIB Cel ) gene promoters require CelR for transcriptional activation in response to cellobiose, but readthrough from the celA promoter contributes to expression of the EII Cel genes; (ii) the EII Cel subunits were required for growth on cellobiose and for transcriptional activation of the cel genes; (iii) CcpA plays little direct role in catabolite repression of the cel regulon, but loss of specific PTS permeases alleviated repression of cel genes in the presence of preferred carbohydrates; and (iv) glucose could induce transcription of the cel regulon when transported by EII Cel . CelR derivatives containing amino acid substitutions for five conserved histidine residues in two PTS regulatory domains and an EIIA-like domain also provided important insights regarding the function of this regulator. Based on these data, a model for the involvement of PTS permeases and the general PTS proteins enzyme I and HPr was developed that reveals a critical role for the PTS in CcpAindependent catabolite repression and induction of cel gene expression in S. mutans.The pathogen primarily responsible for human tooth decay, Streptococcus mutans, can utilize a wide variety of carbohydrates found in the diet and in host-derived macromolecules (6, 16). The S. mutans genome contains more than a dozen phosphoenolpyruvate (PEP)-dependent sugar phosphotransferase system (PTS) permeases dedicated to the internalization and phosphorylation of simple sugars (22,26,27). S. mutans depends on the PTS for the acquisition of energy sources and for acid production through glycolysis, an integral part of its pathogenic mechanisms. A recent study probing the expression of various PTS permeases in S. mutans cells grown in a variety of carbohydrates supports that most of these permeases are subject to transcriptional regulation (5).S. mutans can assimilate a number of ␤-glucosides, including cellobiose, esculin, arbutin, and salicin (8, 21). Cellobiose utilization pathways have been of particular interest because of their potential for the development of alternative energy sources (9, 23). A previous study identified a genetic locus in S. mutans UA159 that is required for the catabolism of cellobiose, including genes for phospho-␤-glucosidase (celA), a putative transcriptional regulator (celR), and the B, A, and C domains of the cellobiose PTS enzyme EII Cel (celB, celC, and celD), respectively (21). Deletion of celA or celD resulted in loss of growth on cellobiose. Hence, utilization of cellobiose by S. mutans consis...

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Section: Discussionsupporting

confidence: 70%

Transcriptional Regulation of the Cellobiose Operon of Streptococcus mutans

2009

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“…Examination of cbpA mRNA levels in an in-frame deletion mutant with deletions in both hk06 and rr06 in D39 showed that this mutant produced cbpA mRNA levels similar to the wild-type levels. This is perhaps not surprising in light of a recent study of S. pneumoniae which showed that a deletion mutant with a mutation in either RR08 or the whole TCS08 resulted in no alteration of the mRNA expression profile, whereas an activating HK08 mutation did alter the profile (22). This suggests that loss-of-function TCSTS mutations do not always influence the expression of regulated genes.…”

Section: Discussionmentioning

confidence: 69%

The Pneumococcal Two-Component Signal Transduction System RR/HK06 Regulates CbpA and PspA by Two Distinct Mechanisms

2007

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We have previously shown that CbpA, a major pneumococcal virulence factor, is regulated by the twocomponent signal transduction system RR/HK06 (A. J. Standish, U. H. Stroeher, and J. C. Paton, Proc. Natl. Acad. Sci. USA 102:7701-7706, 2005). However, additional unidentified regulated factors appeared to be responsible for differences in adherence and the ability of Streptococcus pneumoniae to cause disease in a mouse model. Here, we identified a number of other regulated genes by overexpressing the system. cbpA, along with a cotranscribed upstream gene, showed substantial increases in expression when RR06 was overexpressed in S. pneumoniae strains D39 and TIGR4. However, there were no other similarities between these strains. In D39, rr06 overexpression decreased expression of numerous factors, including the major virulence factor gene pspA. Further investigation of cbpA regulation by RR/HK06, using mutants with mutations in both HK06 and RR06, suggested that rather than the norm, cbpA transcription was activated when RR06 was in the nonphosphorylated form. Although other factors, such as pspA and gls24, are regulated by this system, these genes appear to be repressed when RR06 is in its phosphorylated form.

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“…Although the mechanism is unclear, there are many precedents. For example, the inactivation of the sensor kinase of the TCS08 TCS of Streptococcus pneumoniae leads to the down-regulation of the genes involved with cellobiose utilization, but the inactivation of the cognate response regulator has no effect (34). Similarly, the inactivation of the CiaR response regulator of S. mutans has little effect on mutacin I production, whereas the inactivation of CiaH, the cognate sensor kinase, abolishes mutacin I production (39).…”

Section: Discussionmentioning

confidence: 99%

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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The Two-Component Regulatory System TCS08 Is Involved in Cellobiose Metabolism ofStreptococcus pneumoniaeR6

Cited by 54 publications

References 46 publications

Transcriptional Regulation of the Cellobiose Operon of Streptococcus mutans

Transcriptional Regulation of the Cellobiose Operon of Streptococcus mutans

The Pneumococcal Two-Component Signal Transduction System RR/HK06 Regulates CbpA and PspA by Two Distinct Mechanisms

LiaS Regulates Virulence Factor Expression in Streptococcus mutans

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