Organization around the dnaA gene of Streptococcus pneumoniae

Gasc, Anne-Marie; Giammarinaro, Philippe; Richter, Stefan; Sicard, Michel

doi:10.1099/00221287-144-2-433

Cited by 26 publications

(24 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the downstream gene spoJ would appear to be the most likely candidate for this role, our preliminary experiments have not shown that the deletion of spoJ either affects competence in a wild-type background or restores competence to a CiaH-activated strain (data not shown). While we cannot exclude the possibility that spoJ may affect the development of competence under other conditions not tested, it is also notable that the htrA-spoJ locus lies adjacent to the putative origin of replication of the pneumococcal chromosome (16,21,54). A polar effect related to the initiation of DNA replication, similar to that suggested by Claverys et al (8), might be postulated to result from changes in transcriptional activity in this region.…”

Section: Discussionmentioning

confidence: 65%

Pneumococcal HtrA Protease Mediates Inhibition of Competence by the CiaRH Two-Component Signaling System

Sebert¹,

Patel²,

Plotnick

et al. 2005

J Bacteriol

View full text Add to dashboard Cite

Activation of the CiaRH two-component signaling system prevents the development of competence for genetic transformation in Streptococcus pneumoniae through a previously unknown mechanism. Earlier studies have shown that CiaRH controls the expression of htrA, which we show encodes a surface-expressed serine protease. We found that mutagenesis of the putative catalytic serine of HtrA, while not impacting the competence of a ciaRH ؉ strain, restored a normal competence profile to a strain having a mutation that constitutively activates the CiaH histidine kinase. This result implies that activity of HtrA is necessary for the CiaRH system to inhibit competence. Consistent with this finding, recombinant HtrA (rHtrA) decreased the competence of pneumococcal cultures. The rHtrA-mediated decline in transformation efficiency could not be corrected with excess competence-stimulating peptide (CSP), suggesting that HtrA does not act through degradation of this signaling molecule. The inhibitory effects of rHtrA and activated CiaH, however, were largely overcome in a strain having constitutive activation of the competence pathway through a mutation in the cytoplasmic domain of the ComD histidine kinase. Although these results suggested that HtrA might act through degradation of the extracellular portion of the ComD receptor, Western immunoblots for ComD did not reveal changes in protein levels attributable to HtrA. We therefore postulate that HtrA may act on an unknown protein target that potentiates the activation of the ComDE system by CSP. These findings suggest a novel regulatory role for pneumococcal HtrA in modulating the activity of a two-component signaling system that controls the development of genetic competence.Competence for genetic transformation in the gram-positive human pathogen Streptococcus pneumoniae is a tightly regulated process, influenced by factors including bacterial cell density, pH, and temperature (5, 57-60). Much has been learned recently about the density-dependent initiation of competence orchestrated by the peptide quorum-sensing system encoded by comCDE and comAB (reviewed in reference 7). The product of comC is a small peptide precursor that is exported from the bacterium and thought to be concurrently processed to form the mature 17-amino-acid competence-stimulating peptide (CSP) by the ComAB transporter (18,19,22). The transmembrane ComD histidine kinase is then stimulated by extracellular CSP and activates its cognate ComE response regulator, which in turn initiates a transcriptional cascade resulting in DNA uptake and recombination (20,43). ComE also promotes the transcription of comCDE and comAB (62), resulting in positive feedback that amplifies signaling through the system. Less is understood, however, about the mechanisms that then shut off competence (7)-even as the bacterial density continues to increase-or the adaptive function of limiting competence expression to such a narrow window of growth.

show abstract

Section: Discussionmentioning

confidence: 65%

Pneumococcal HtrA Protease Mediates Inhibition of Competence by the CiaRH Two-Component Signaling System

Sebert¹,

Patel²,

Plotnick

et al. 2005

J Bacteriol

View full text Add to dashboard Cite

show abstract

“…As was shown to be the case for htrA of S. pneumoniae (12,47) and S. pyogenes (11,28), htrA of S. mutans is near the apparent origin of chromosome replication. Immediately downstream of htrA, genes homologous to spo0J and dnaA were identified.…”

Section: Discussionmentioning

confidence: 71%

“…DnaA boxes, which are bound by DnaA proteins to form the initiation complex for chromosome replication were identified in this region. Similar to those of S. pneumoniae (12) and S. pyogenes (28), the DnaA boxes of S. mutans are localized to untranslated regions upstream of htrA and upstream and downstream of dnaA (Fig. 1).…”

Section: Discussionmentioning

confidence: 76%

Role of HtrA in Growth and Competence of Streptococcus mutans UA159

2005

View full text Add to dashboard Cite

We report here that HtrA plays a role in controlling growth and competence development for genetic transformation in Streptococcus mutans. Disruption of the gene for HtrA resulted in slow growth at 37°C, reduced thermal tolerance at 42°C, and altered sucrose-dependent biofilm formation on polystyrene surfaces. The htrA mutant also displayed a significantly reduced ability to undergo genetic transformation. A direct association between HtrA and genetic competence was demonstrated by the increased expression of the htrA gene upon exposure to competence-stimulating peptide. The induction of htrA gradually reached a maximum at around 20 min, suggesting that HtrA may be involved in a late competence response. Complementation of the htrA mutation in a single copy on the chromosome of the mutant could rescue the defective growth phenotypes but not transformability, apparently because a second gene, spo0J, immediately downstream of htrA, also affects transformation. The htrA and spo0J genes were shown to be both individually transcribed and cotranscribed and probably have a functional connection in competence development. HtrA regulation appears to be finely tuned in S. mutans, since strains containing multiple copies of htrA exhibited abnormal growth phenotypes. Collectively, the results reveal HtrA to be an integral component of the regulatory network connecting cellular growth, stress tolerance, biofilm formation, and competence development and reveal a novel role for the spo0J gene in genetic transformation.

show abstract

“…The genomic origin of replication has not been experimentally identified in S. pneumoniae; however, based on the presence of clusters of DnaA boxes and other genomic features, we hypothesize that the S. pneumoniae origin of DNA replication is upstream of dnaA, which is gene spr0001 in our nomenclature system (16).…”

Section: Resultsmentioning

confidence: 97%

Genome of the Bacterium Streptococcus pneumoniae Strain R6

Hoskins¹,

Alborn²,

et al. 2001

View full text Add to dashboard Cite

Streptococcus pneumoniae is among the most significant causes of bacterial disease in humans. Here we report the 2,038,615-bp genomic sequence of the gram-positive bacterium S. pneumoniae R6. Because the R6 strain is avirulent and, more importantly, because it is readily transformed with DNA from homologous species and many heterologous species, it is the principal platform for investigation of the biology of this important pathogen. It is also used as a primary vehicle for genomics-based development of antibiotics for gram-positive bacteria. In our analysis of the genome, we identified a large number of new uncharacterized genes predicted to encode proteins that either reside on the surface of the cell or are secreted. Among those proteins there may be new targets for vaccine and antibiotic development.

show abstract

Organization around the dnaA gene of Streptococcus pneumoniae

Cited by 26 publications

References 41 publications

Pneumococcal HtrA Protease Mediates Inhibition of Competence by the CiaRH Two-Component Signaling System

Pneumococcal HtrA Protease Mediates Inhibition of Competence by the CiaRH Two-Component Signaling System

Role of HtrA in Growth and Competence of Streptococcus mutans UA159

Genome of the Bacterium Streptococcus pneumoniae Strain R6

Contact Info

Product

Resources

About