Pneumococcal-Driven Genetic Competence: A Key Driver of Pathobiont Adaptation and Disease Potential

High genetic variability in streptococci is driven by natural competence, specifically in Streptococcus pneumoniae and its close commensal species (Streptococcus pseudopneumoniae, Streptococcus oralis, and Streptococcus mitis), which drives rapid Streptococcal evolution. The genome of S. pneumoniae and its close commensal species exhibits high interspecies recombination, an open-pan genome, and a similar evolutionary origin. Mechanisms of natural competence are a highly regulated process driven by numerous molecular players at different stages. Natural competence in Streptococci drives the shift from commensal to pathogenic state. Streptococcus pneumoniae acquires various virulence and antibiotic-resistant genes (ARGs) via natural competence and also facilitates immune evasion, the emergence of multidrug-resistant strains, and capsule switching between strains. Most reports indicated that the natural competence in S. pneumoniae is a one-way street process; however, a few studies have proved that it is a two-way street process. The purpose of the current review is to elucidate (i) the genome of S. pneumoniae and its close relatives, (ii) the mechanism of HGT, (iii) HGT in S. pneumoniae and related commensal species, (iv) acquisition of drug-resistance genes and virulence factors, and (v) the implication of HGT in competence-driven gene transfer in IPD and interaction between host and pathogens.