Genetic diversity and evolutionary adaptation of Clostridium paraputrificum, a rare pathogen in humans

Clostridium paraputrificum infection in humans is extremely rare, and its pathogenesis and evolutionary mechanisms remain poorly understood. We sequenced the genome of strain CP_SH01 isolated from the blood culture of an ICU patient with acute abdominal injury and bloodstream infection. The genome harbored an intact prophage and ten insertion-sequence elements. Genome-wide metabolic reconstruction uncovered 42 fully complete modules linked to the utilization of different sugars and fermentation. Phylogenomic analysis of 42 global strains revealed two clades with substantial genetic diversity. A comparative genomic analysis was carried out to decode the pangenomic structure of C. paraputrificum, and functional differences between 2,434 core genes and 5,939 accessory genes. Meanwhile, 52 genes linked to 16 virulence factors and 15 antimicrobial resistance genes were identified. The majority of these clinically relevant genes, especially drug-resistant genes, were accessory and likely acquired via possible horizontal transfer. Additionally, genes under positive Darwinian selection were identified, potentially crucial for bacterial adaptation and immune interaction. This study presents the first blood-derived C. paraputrificum genome, revealing the global distribution of virulence and resistance genes. The accessory genome serves as a reservoir for clinically relevant traits, and positively selected genes provide insights into adaptive evolution and pathogenicity.