Parallel Evolution of Streptococcus pneumoniae and Streptococcus mitis to Pathogenic and Mutualistic Lifestyles

ABSTRACT The bacterium Streptococcus pneumoniae is one of the leading causes of fatal infections affecting humans. Intriguingly, phylogenetic analysis shows that the species constitutes one evolutionary lineage in a cluster of the otherwise commensal Streptococcus mitis strains, with which humans live in harmony. In a comparative analysis of 35 genomes, including phylogenetic analyses of all predicted genes, we have shown that the pathogenic pneumococcus has evolved into a master of genomic flexibility while lineages that evolved into the nonpathogenic S. mitis secured harmonious coexistence with their host by stabilizing an approximately 15%-reduced genome devoid of many virulence genes. Our data further provide evidence that interspecies gene transfer between S. pneumoniae and S. mitis occurs in a unidirectional manner, i.e., from S. mitis to S. pneumoniae. Import of genes from S. mitis and other mitis, anginosus, and salivarius group streptococci ensured allelic replacements and antigenic diversification and has been driving the evolution of the remarkable structural diversity of capsular polysaccharides of S. pneumoniae. Our study explains how the unique structural diversity of the pneumococcal capsule emerged and conceivably will continue to increase and reveals a striking example of the fragile border between the commensal and pathogenic lifestyles. While genomic plasticity enabling quick adaptation to environmental stress is a necessity for the pathogenic streptococci, the commensal lifestyle benefits from stability. IMPORTANCE One of the leading causes of fatal infections affecting humans, Streptococcus pneumoniae, and the commensal Streptococcus mitis are closely related obligate symbionts associated with hominids. Faced with a shortage of accessible hosts, the two opposing lifestyles evolved in parallel. We have shown that the nonpathogenic S. mitis secured harmonious coexistence with its host by stabilizing a reduced genome devoid of many virulence genes. Meanwhile, the pathogenic pneumococcus evolved into a master of genomic flexibility and imports genes from S. mitis and other related streptococci. This process ensured antigenic diversification and has been driving the evolution of the remarkable structural diversity of capsular polysaccharides of S. pneumoniae, which conceivably will continue to increase and present a challenge to disease prevention.