Complete genome sequence of the emerging pathogen Cysteiniphilum spp. and comparative genomic analysis with genus Francisella: Insights into its genetic diversity and potential virulence traits

Cysteiniphilum is a newly discovered genus in 2017 and is phylogenetically closely related to highly pathogenic Francisella tularensis. Recently, it has become an emerging pathogen in humans. However, the complete genome sequence of genus Cysteiniphilum is lacking, and the genomic characteristics of genetic diversity, evolutionary dynamics, and pathogenicity have not been characterized. In this study, the complete genome of the first reported clinical isolate QT6929 of genus Cysteiniphilum was sequenced, and comparative genomics analyses to Francisella genus were conducted to unveil the genomic landscape and diversity of the genus Cysteiniphilum. Our results showed that the complete genome of QT6929 consists of one 2.61 Mb chromosome and a 76,819 bp plasmid. The calculated average nucleotide identity and DNA-DNA hybridization values revealed that two clinical isolates QT6929 and JM-1 should be reclassified as two novel species in genus Cysteiniphilum. Pan-genome analysis revealed genomic diversity within the genus Cysteiniphilum and an open pan-genome state. Genomic plasticity analysis exhibited abundant mobile genetic elements including genome islands, insertion sequences, prophages, and plasmids on Cysteiniphilum genomes, which facilitated the broad exchange of genetic material between Cysteiniphilum and other genera like Francisella and Legionella. Several potential virulence genes associated with lipopolysaccharide/lipooligosaccharide, capsule, and haem biosynthesis specific to clinical isolates were predicted and might contribute to their pathogenicity in humans. Incomplete Francisella pathogenicity island was identified in most Cysteiniphilum genomes. Overall, our study provides an updated phylogenomic relationship of members of the genus Cysteiniphilum and comprehensive genomic insights into this rare emerging pathogen.