Abstract
The two-component regulatory system CiaRH of Streptococcus pneumoniae is involved in β-lactam resistance, maintenance of cell integrity, bacteriocin production, host colonization, virulence, and competence. The response regulator CiaR controls, among other genes, expression of five highly similar small non-coding RNAs, designated csRNAs. These csRNAs control competence development by targeting comC, encoding the precursor of the competence stimulating peptide, which is essential to initiate the regulatory cascade leading to competence. In addition, another gene product of the CiaR regulon, the serine protease HtrA, is also involved in competence control. In the absence of HtrA, five csRNAs could suppress competence, but one csRNA alone was not effective. To determine if all csRNAs are needed, reporter gene fusions to competence genes were used to monitor competence gene expression in the presence of different csRNAs. These experiments showed that two csRNAs were not enough to prevent competence, but combinations of three csRNAs, csRNA1,2,3, or csRNA1,2,4 were sufficient. In S. pneumoniae strains expressing only csRNA5, a surprising positive effect was detected on the level of early competence gene expression. Hence, the role of the csRNAs in competence regulation is more complex than anticipated. Mutations in comC (comC8) partially disrupting predicted complementarity to the csRNAs led to competence even in the presence of all csRNAs. Reconstitution of csRNA complementarity to comC8 restored competence suppression. Again, more than one csRNA was needed. In this case, even two mutated csRNAs complementary to comC8, csRNA1–8 and csRNA2–8, were suppressive. In conclusion, competence in S. pneumoniae is additively controlled by the csRNAs via post-transcriptional regulation of comC.
Highlights
The human pathogen Streptococcus pneumoniae shows a remarkable genomic plasticity (Croucher et al, 2012, 2014) and is a paradigm for bacteria that are able to undergo natural genetic transformation
The comC8 mutant allele uncoupling competence development from csRNA control (Schnorpfeil et al, 2013) was introduced into a csRNA- and HtrA-deficient strain (RKL558, Table 1), which had been transformed with rpsl41 DNA to yield a streptomycin resistant derivative (RKL362)
Transformation experiments performed in competence nonpermissive BHI medium showed that inactivation of HtrA deficient (htrA) and the csRNA genes ccnA-D is needed to allow competence to develop (Schnorpfeil et al, 2013)
Summary
The human pathogen Streptococcus pneumoniae shows a remarkable genomic plasticity (Croucher et al, 2012, 2014) and is a paradigm for bacteria that are able to undergo natural genetic transformation (for recent reviews see Johnston et al, 2014; Straume et al, 2014). The ability of S. pneumoniae to develop genetic competence is a highly regulated process depending on a variety of internal and external signals. Of these signals, the secreted peptide pheromone CSP The identical genes comX1/comX2 in turn encode the alternative sigma factor ComX, which directs transcription of late competence genes (Lee and Morrison, 1999). Proteins encoded by this class of genes are required for uptake of DNA and subsequent recombination (Claverys et al, 2009; Laurenceau et al, 2013)
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