Identification of <i>Streptococcus suis</i> putative zoonotic virulence factors: a systematic review and genomic meta-analysis

<i>Streptococcus suis</i> is an emerging zoonotic pathogen. Over 100 putative virulence factors have been described, but it is unclear to what extent these virulence factors could contribute to zoonotic potential of <i>S. suis</i>. We identified all <i>S. suis</i> virulence factors studied in experimental models of human origin in a systematic review and assessed their contribution to zoonotic potential in a subsequent genomic meta-analysis. PubMed and Scopus were searched for English-language articles that studied <i>S. suis</i> virulence published until March 31, 2021. Articles that analyzed a virulence factor by knockout mutation, purified protein, and/or recombinant protein in a model of human origin, were included. Data on virulence factor, strain characteristics, used human models and experimental outcomes were extracted. All publicly available <i>S. suis</i> genomes with available metadata on host, disease status and country of origin, were included in a genomic meta-analysis. We calculated the ratio of the prevalence of each virulence factor in human and pig isolates. We included 130 articles and 1703 <i>S. suis</i> genomes in the analysis. We identified 53 putative virulence factors that were encoded by genes which are part of the <i>S. suis</i> core genome and 26 factors that were at least twice as prevalent in human isolates as in pig isolates. Hhly3 and NisK/R were particularly enriched in human isolates, after stratification by genetic lineage and country of isolation. This systematic review and genomic meta-analysis has identified virulence factors that are likely to contribute to the zoonotic potential of <i>S. suis</i>.