Tackling the Regulation of Pneumococcal Fitness and Virulence Factors

Streptococcus pneumoniae is a commensal of the human upper respiratory tract and the etiological agent of several life-threatening diseases. This pathogen is the model bacterium for natural competence. Furthermore, the pneumococci played an important role in the identification of DNA as the main molecule involved in bacterial transformation. As a result, studies on the pneumococcal genome provided an initial overview of the genetic potential of this pathogen. The pneumococcus is a highly versatile bacterium possessing a high rate of uptake and recombination of exogenous DNA from neighboring bacteria. As such, a significant diversity in the genome content among the different pneumococcal strains has been reported. The capsular polysaccharide, an important pneumococcal virulence factor, is the best example on the pneumococcal diversity. There are over 98 serotypes characterized to date presenting differences in their capsule (cps) locus. Additional to the cps locus, the pneumococcus also presents 13 genomic islets annotated as regions of diversity (RD) encoded in the auxiliary genome. Remarkably, 8 of the pneumococcal RD studied so far have been associated with virulence. Furthermore, the ongoing sequencing of over 4000 pneumococcal genomes have shed light on the conservation level of well-known pneumococcal virulence factors. Interestingly, important pneumococcal virulence determinants show variations in the gene and protein sequence among the different strains. Prototypes are for example the pneumococcal surface protein C (PspC) and pneumococcal adherence and virulence factor B (PavB). Conversely, gene regulation in S. pneumoniae is carried out by highly conserved and genome- wide distributed transcriptional factors. Overall, the pneumococci interplays with its environment with 4 major regulatory systems: quorum sensing (QS), stand-alone transcriptional regulators, small RNAs (sRNAs) and two-component regulatory systems (TCS). Some of these systems are multifaceted and share more than one feature. Furthermore, ...