Dataset Information

Convergence of regulatory networks on the pilus locus of Streptococcus pneumoniae.

ABSTRACT: The rlrA pilus locus of Streptococcus pneumoniae is an example of a pathogenicity island acquired through genetic recombination. Many acquired genetic elements commandeer preexisting networks of the new organism for transcriptional regulation. We hypothesized that the rlrA locus has integrated into transcriptional regulatory networks controlling expression of virulence factors important in adhesion and invasion. To test this hypothesis, we determined the impact on pilus expression of known regulators controlling adherence, including the two-component systems CbpR/S and HK/RR03 and the transcriptional regulators of divalent cation transporters MerR and PsaR in vitro and in vivo. It was determined that the pilus locus is down-regulated by preexisting networks designed for adhesion and cation transport/response and that its regulation occurs through RlrA. The pilus locus was found to participate in invasion specifically restricted to lung epithelial cells in vitro. While expression of pili had only a small effect on virulence with an intranasal infection model, pili were critically important with an intratracheal infection model. Thus, expression of pili appears to have become integrated into the regulatory circuits for lung-specific invasion by pneumococci.

SUBMITTER: Rosch JW

PROVIDER: S-EPMC2446684 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Convergence of regulatory networks on the pilus locus of Streptococcus pneumoniae.

Rosch Jason W JW Mann Beth B Thornton Justin J Sublett Jack J Tuomanen Elaine E

Infection and immunity 20080428 7

The rlrA pilus locus of Streptococcus pneumoniae is an example of a pathogenicity island acquired through genetic recombination. Many acquired genetic elements commandeer preexisting networks of the new organism for transcriptional regulation. We hypothesized that the rlrA locus has integrated into transcriptional regulatory networks controlling expression of virulence factors important in adhesion and invasion. To test this hypothesis, we determined the impact on pilus expression of known regul ...[more]

PMID: 18443093

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Project description:The Streptococcus pneumoniae pilus-1 is encoded by pilus islet 1 (PI-1), which has three clonal variants (clade I, II and III) and is present in about 30% of clinical pneumococcal isolates. In vitro and in vivo assays have demonstrated that pilus-1 is involved in attachment to epithelial cells and virulence, as well as protection in mouse models of infection. Several reports suggest that pilus-1 expression is tightly regulated and involves the interplay of numerous genetic regulators, including the PI-1 positive regulator RlrA. In this report we provide evidence that pilus expression, when analyzed at the single-cell level in PI-1 positive strains, is biphasic. In fact, the strains present two phenotypically different sub-populations of bacteria, one that expresses the pilus, while the other does not. The proportions of these two phenotypes are variable among the strains tested and are not influenced by genotype, serotype, growth conditions, colony morphology or by the presence of antibodies directed toward the pilus components. Two sub-populations, enriched in pilus expressing or not expressing bacteria were obtained by means of colony selection and immuno-detection methods for five strains. PI-1 sequencing in the two sub-populations revealed the absence of mutations, thus indicating that the biphasic expression observed is not due to a genetic modification within PI-1. Microarray expression profile and western blot analyses on whole bacterial lysates performed comparing the two enriched sub-populations, revealed that pilus expression is regulated at the transcriptional level (on/off regulation), and that there are no other genes, in addition to those encoded by PI-1, concurrently regulated across the strains tested. Finally, we provide evidence that the over-expression of the RrlA positive regulator is sufficient to induce pilus expression in pilus-1 negative bacteria. Overall, the data presented here suggest that the observed biphasic pilus expression phenotype could be an example of bistability in pneumococcus.

Dataset Information

Convergence of regulatory networks on the pilus locus of Streptococcus pneumoniae.

Publications

Convergence of regulatory networks on the pilus locus of Streptococcus pneumoniae.

Similar Datasets

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