Competence in Streptococcus pneumoniae and Close Commensal Relatives: Mechanisms and Implications

Abstract

The mitis group of streptococci comprises species that are common colonizers of the naso-oral-pharyngeal tract of humans. Streptococcus pneumoniae and Streptococcus mitis are close relatives and share ~60-80% of orthologous genes, but still present striking differences in pathogenic potential toward the human host. S. mitis has long been recognized as a reservoir of antibiotic resistance genes for S. pneumoniae, as well as a source for capsule polysaccharide variation, leading to resistance and vaccine escape. Both species share the ability to become naturally competent, and in this context, competence-associated killing mechanisms such as fratricide are thought to play an important role in interspecies gene exchange. Here, we explore the general mechanism of natural genetic transformation in the two species and touch upon the fundamental clinical and evolutionary implications of sharing similar competence, fratricide mechanisms, and a large fraction of their genomic DNA.

Keywords: CSP; Streptococcus pneumoniae; competence; natural genetic transformation; streptococcus.

Figure 1

Schematic representation of competence gene regulation in S. pneumoniae and S. mitis. Pre-CSP is processed and exported by the ABC-transporter ComAB. CSP is detected by the histidine kinase ComD, which phosphorylates ComE. Phosphorylated ComE promotes the transcription of comAB, comCDE and sigX, in addition to other early genes. SigX regulates the expression of the DNA uptake and transformasome machineries, as well as the production of killing factors against other cells. In S. pneumoniae and S. mitis, fratricide depends on the late competence protein CbpD that lyses non-competent cells in the shared environment. Competent cells produce the early competence protein ComM, protecting themselves from CbpD lytic activity. Competent S. pneumoniae cells also produce CibAB, a two-peptide bacteriocin that acts on the membrane of non-competent cells. CibC is produced by competent cells in order to confer protection from the bacteriocin activity. Competent cells are then exposed to DNA released from the target cells that can be integrated into their genomes by homologous recombination. Competent S. mitis cells produce a different set of bacteriocins than S. pneumoniae under SigX regulation.

Figure 2

ComC polymorphism among 22 S. mitis strains and S. pneumoniae CSP-1 and CSP-2. Blue colors the residues according to the percentage of the residues in each column that agree with the consensus sequence. Only the residues that agree with the consensus residue for each column are colored. The black arrow indicates the CSP processing site. Full CSP sequences for available strains were obtained from Kilian et al. (2008).