Comparative genomic analysis of the emerging pathogen Streptococcus pseudopneumoniae: novel insights into virulence determinants and identification of a novel species-specific molecular marker

Abstract

Streptococcus pseudopneumoniae is a close relative of the major human pathogen S. pneumoniae. While initially considered as a commensal species, it has been increasingly associated with lower-respiratory tract infections and 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 phylogenetic and comparative genomic analyses of SMG genomes, we identified a new molecular marker specific for S. pseudopneumoniae and absent from any other bacterial genome sequenced to date. We found that a large number of known virulence and colonization genes are present in the core S. pseudopneumoniae genome and we reveal the impressive number of known and new surface-exposed proteins encoded by this species. 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 resistances, were encoded by Tn916-like integrating conjugative elements and Mega-2. Overall, we found a tight association of genotypic determinants of AMR as well as phenotypic AMR with a specific lineage of S. pseudopneumoniae. Taken together, our results sheds 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.\n\nImportanceS. 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 means to distinguish it from S. pneumoniae. Here, we provide a new molecular marker entirely specific for S. pseudopneumoniae. Furthermore, our research provides a deep analysis of the presence of virulence and colonization genes, as well as AMR determinants in this species. Our results provide crucial information and pave the way for further studies aiming at understanding the pathogenesis and epidemiology of S. pseudopneumoniae.