Genomic Characterization of the Emerging Pathogen Streptococcus pseudopneumoniae

S. pseudopneumoniae is an overlooked pathogen emerging as the causative agent of lower-respiratory-tract infections and associated with chronic obstructive pulmonary disease (COPD) and exacerbation of COPD. However, much remains unknown on its clinical importance and epidemiology, mainly due to the lack of specific markers to distinguish it from S. pneumoniae. Here, we provide a new molecular marker entirely specific for S. pseudopneumoniae and offer a comprehensive view of the virulence and colonization genes found in this species. Finally, our results pave the way for further studies aiming at understanding the pathogenesis and epidemiology of S. pseudopneumoniae.Streptococcus pseudopneumoniae is a close relative of the major human pathogen S. pneumoniae. It is increasingly associated with lower-respiratory-tract infections (LRTI) and a high prevalence of antimicrobial resistance (AMR). S. pseudopneumoniae is difficult to identify using traditional typing methods due to similarities with S. pneumoniae and other members of the mitis group (SMG). Using whole-genome sequencing of LRTI isolates and a comparative genomic approach, we found that a large number of pneumococcal virulence and colonization genes are present in the core S. pseudopneumoniae genome. We also reveal an impressive number of novel surface-exposed proteins encoded by the genome of this species. In addition, we propose a new and entirely specific molecular marker useful for the identification of S. pseudopneumoniae. Phylogenetic analyses of S. pseudopneumoniae show that specific clades are associated with allelic variants of core proteins. Resistance to tetracycline and macrolides, the two most common types of resistance, were found to be encoded by Tn916-like integrating conjugative elements and Mega-2. Overall, we found a tight association of genotypic determinants of AMR and phenotypic AMR with a specific lineage of S. pseudopneumoniae. Taken together, our results shed light on the distribution in S. pseudopneumoniae of genes known to be important during invasive disease and colonization and provide insight into features that could contribute to virulence, colonization, and adaptation