The two-component signal transduction system RR06/HK06 regulates expression of
            <i>cbpA</i>
            in
            <i>Streptococcus pneumoniae</i>

Standish, Alister; Stroeher, Uwe H.; Paton, James C.

doi:10.1073/pnas.0409377102

Cited by 41 publications

(61 citation statements)

References 38 publications

(37 reference statements)

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“…For instance, CiaR/ CiaH has been demonstrated to contribute to virulence (25,29), probably in part through control of expression of htrA, which encodes a serine protease that is a major virulence factor (11,19). Recently, TCS06 has been found to regulate the expression of cbpA, which codes for a major adhesin that is also a protective antigen (26).…”

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confidence: 99%

Regulation of Gene Expression inStreptococcus pneumoniaeby Response Regulator 09 Is Strain Dependent

et al. 2007

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Recent murine studies have demonstrated that the role of response regulator 09 (RR09) of Streptococcus pneumoniae in virulence is different in different strains. In the present study, we used a murine pneumonia model of infection to assess the virulence of a TIGR4 rr09 mutant, and we found that TIGR4⌬rr09 was attenuated after intranasal infection. Furthermore, we investigated the in vitro transcriptional changes in pneumococcal rr09 mutants of two strains, D39 and TIGR4, by microarray analysis. The transcriptional profiles of the rr09 mutants of both strains had clear differences compared to the profiles of the parental wild-type strains. In D39⌬rr09, but not in TIGR4⌬rr09, genes involved in competence (e.g., comAB) were upregulated. In TIGR4, genes located on the rlrA pathogenicity islet, which are not present in the D39 genome, appeared to be regulated by RR09. Furthermore, several phosphotransferase systems (PTSs) believed to be involved in sugar uptake (e.g., the PTS encoded by sp0060 to sp0066) were strongly downregulated in D39⌬rr09, while they were not regulated by RR09 in TIGR4. To examine the role of one of these PTSs in virulence, D39⌬sp0063 was constructed and tested in a murine infection model. No difference between the virulence of this strain and the virulence of the wild type was found, indicating that downregulation of the sp0063 gene alone is not the cause of the avirulent phenotype of D39⌬rr09. Finally, expression of rr09 and expression of three of our identified RR09 targets during infection in mice were assessed. This in vivo experiment confirmed that there were differences between expression in wild-type strain TIGR4 and expression in the rr09 mutant, as well as differences between expression in wild-type strain D39 and expression in wild-type strain TIGR4. In conclusion, our results indicate that there is strain-specific regulation of pneumococcal gene expression by RR09.

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Regulation of Gene Expression inStreptococcus pneumoniaeby Response Regulator 09 Is Strain Dependent

et al. 2007

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“…which is induced by the autoinducible peptide BlpC and controls bacteriocin production (6,32); TCS04, which is involved in the regulation of PsaA (23); and TCS06, which regulates expression of cbpA (35). The only essential response regulator, RR02, regulates expression of PspA (25), and the orphan response regulator, RitR, regulates iron transport (41).…”

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

McKessar

Hakenbeck

2007

J Bacteriol

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The two-component system TCS08 is one of the regulatory systems that is important for virulence of Streptococcus pneumoniae. In order to investigate the TCS08 regulon, we have analyzed transcription profiles of mutants derived from S. pneumoniae R6 by microarray analysis. Since deletion mutants are often without a significant phenotype, we constructed a mutation in the histidine kinase HK08, T133P, in analogy to the phosphatase mutation T230P in the H box of the S. pneumoniae CiaH kinase described recently (D. Zähner, K. Kaminski, M. van der Linden, T. Mascher, M. Merai, and R. Hakenbeck, J. Mol. Microbiol. Biotechnol. 4:211-216, 2002). In addition, a deletion mutation was constructed in rr08, encoding the cognate response regulator. The most heavily suppressed genes in the hk08 mutant were spr0276 to spr0282, encoding a putative cellobiose phosphoenolpyruvate sugar phosphotransferase system (PTS). Whereas the R6 Sm r parent strain and the ⌬rr08 mutant readily grew on cellobiose, the hk08 mutant and selected mutants with deletions in the PTS cluster did not, strongly suggesting that TCS08 is involved in the catabolism of cellobiose. Homologues of the TCS08 system were found in closely related streptococci and other gram-positive cocci. However, the genes spr0276 to spr0282, encoding the putative cellobiose PTS, represent a genomic island in S. pneumoniae and homologues were found in Streptococcus gordonii only, suggesting that this system might contribute to the pathogenicity potential of the pneumococcus.

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“…A previous study reported that the rr06/hk06 locus is involved in regulating the expression of cbpA (53). We determined if this TCS regulated expression of other pneumococcal genes and virulence factors by transcriptional analysis of an rr06 mutant in laboratory strain R6 by microarray analysis.…”

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confidence: 99%

RR06 Activates Transcription of spr1996 andcbpAinStreptococcus pneumoniae

Zhang

2007

J Bacteriol

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Streptococcus pneumoniae colonizes at the nasopharynx of humans and is able to disseminate and cause various infections. The hallmark of pneumococcal disease is rapid bacterial replication in different tissue sites leading to intense inflammation. The genetic basis of pneumococcal adaptation to different host niches remains sketchy. In this study, we investigated the regulatory effect of RR06, a response regulator protein, on gene expression of S. pneumoniae. Microarray and Northern blot analyses showed that RR06 is specifically required for transcription of spr1996 and cbpA. While the function of Spr1996 is unknown, CbpA has been well characterized as a surface-exposed protective antigen and a virulence factor of S. pneumoniae. A recombinant form of RR06 was able to bind to a 19-bp conserved sequence shared by the spr1996 and cbpA promoter regions. Furthermore, inactivation of rr06 resulted in loss of CbpA expression as detected by antibody staining and bacterial adhesion. CbpA expression was restored in trans by the intact rr06 gene. However, a mutant, RR06(D51A), with a point mutation in the aspartate residue at position 51 (a predicted major phosphorylation site) of RR06, completely abolished the CbpA expression, suggesting that RR06 phosphorylation is required for transcriptional activation of spr1996 and cbpA. Finally, inactivation of rr06 in additional pneumococcal strains also led to the loss of CbpA expression. These data implicate that RR06 activates the expression of spr1996 and cbpA in many other pneumococcal strains.

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The two-component signal transduction system RR06/HK06 regulates expression of cbpA in Streptococcus pneumoniae

Cited by 41 publications

References 38 publications

Regulation of Gene Expression inStreptococcus pneumoniaeby Response Regulator 09 Is Strain Dependent

Regulation of Gene Expression inStreptococcus pneumoniaeby Response Regulator 09 Is Strain Dependent

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

RR06 Activates Transcription of spr1996 andcbpAinStreptococcus pneumoniae

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