Contribution of a response regulator to the virulence of Streptococcus pneumoniae is strain dependent.
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ABSTRACT:
SUBMITTER: Blue CE
PROVIDER: S-EPMC166049 | biostudies-other | 2003 Aug
REPOSITORIES: biostudies-other
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Project description: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 TIGR4Deltarr09 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 D39Deltarr09, but not in TIGR4Deltarr09, 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 D39Deltarr09, while they were not regulated by RR09 in TIGR4. To examine the role of one of these PTSs in virulence, D39Deltasp0063 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 D39Deltarr09. 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.
| S-EPMC1797359 | biostudies-literature
Project description:Recent murine studies have demonstrated that the role of response regulator 09 (RR09) of S. pneumoniae in virulence varies between strains. In the present study, we used a murine pneumonia model of infection to assess the virulence of a TIGR4 rr09-mutant, and found that TIGR4Δrr09 was attenuated after intranasal infection. Further, 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 in both strains displayed clear differences compared to their parental wild-type. In D39Δrr09 but not TIGR4Δrr09, genes involved in competence (e.g. comAB) were upregulated. In TIGR4, genes located on the rlrA pathogenicity islet, absent in the D39 genome, appeared to be regulated by RR09. Furthermore, several phosphotransferase systems (PTSs), believed to be involved in sugar uptake (e.g., sp0060-sp0066), were strongly downregulated in D39Δrr09, while not regulated by RR09 in TIGR4. To address the role of one of these PTS in virulence, D39Δsp0063 was constructed and tested in a murine infection model. No difference in virulence compared to the wild-type was found, indicating that downregulation of this gene alone is not the cause of the avirulent phenotype of D39Δrr09. Finally, expression of rr09 and three of our identified RR09 targets were assessed during infection in mice. This in vivo experiment confirmed differences in expression between TIGR4 wild-type and rr09-mutant, as well as between wild-type D39 and TIGR4. In conclusion, our results indicate strain specific regulation of pneumococcal gene expression by RR09. Keywords: Genetic modification
2006-10-28 | GSE6139 | GEO
Project description:Recent murine studies have demonstrated that the role of response regulator 09 (RR09) of S. pneumoniae in virulence varies between strains. In the present study, we used a murine pneumonia model of infection to assess the virulence of a TIGR4 rr09-mutant, and found that TIGR4Δrr09 was attenuated after intranasal infection. Further, 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 in both strains displayed clear differences compared to their parental wild-type. In D39Δrr09 but not TIGR4Δrr09, genes involved in competence (e.g. comAB) were upregulated. In TIGR4, genes located on the rlrA pathogenicity islet, absent in the D39 genome, appeared to be regulated by RR09. Furthermore, several phosphotransferase systems (PTSs), believed to be involved in sugar uptake (e.g., sp0060-sp0066), were strongly downregulated in D39Δrr09, while not regulated by RR09 in TIGR4. To address the role of one of these PTS in virulence, D39Δsp0063 was constructed and tested in a murine infection model. No difference in virulence compared to the wild-type was found, indicating that downregulation of this gene alone is not the cause of the avirulent phenotype of D39Δrr09. Finally, expression of rr09 and three of our identified RR09 targets were assessed during infection in mice. This in vivo experiment confirmed differences in expression between TIGR4 wild-type and rr09-mutant, as well as between wild-type D39 and TIGR4. In conclusion, our results indicate strain-specific regulation of pneumococcal gene expression by RR09. Keywords: genetic modification
2006-12-24 | GSE6137 | GEO
Project description:The transcriptional regulator GlnR of Streptococcus pneumoniae is involved in the regulation of glutamine and glutamate metabolism, controlling the expression of the glnRA and glnPQ-zwf operons, as well as the gdhA gene. To assess the contribution of the GlnR regulon to virulence, D39 wild-type and mutant strains lacking genes of this regulon were tested in an in vitro adherence assay and murine infection models. All of the mutants, except the DeltaglnR mutant, were attenuated in adherence to human pharyngeal epithelial Detroit 562 cells, suggesting a contribution of these genes to adherence during the colonization of humans. During murine colonization, only the DeltaglnA mutant and the glnP-glnA double mutant (DeltaglnAP) were attenuated, in contrast to DeltaglnP, indicating that the effect is caused by the lack of GlnA expression. In our pneumonia model, only DeltaglnP and DeltaglnAP showed a significantly reduced number of bacteria in the lungs and blood, indicating that GlnP is required for survival in the lungs and possibly for dissemination to the blood. In intravenously infected mice, glnP and glnA were individually dispensable for survival in the blood whereas the DeltaglnAP mutant was avirulent. Finally, transcriptome analysis of the DeltaglnAP mutant showed that many genes involved in amino acid metabolism were upregulated. This signifies the importance of glutamine/glutamate uptake and synthesis for full bacterial fitness and virulence. In conclusion, several genes of the GlnR regulon are required at different sites during pathogenesis, with glnA contributing to colonization and survival in the blood and glnP important for survival in the lungs and, possibly, efficient transition from the lungs to the blood.
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