Pathogenomic analysis and characterization of strains recovered from human infections.

is an upper respiratory tract commensal in several mammal and bird species but can also cause severe disease in humans and in production animals such as poultry, cattle, and pigs. In this study, we performed whole-genome sequencing of isolates recovered from a range of human infections, from the mouths of cats, and from wounds on dogs. Together with publicly available genome sequences, we performed phylogenetic and comparative genomic analyses. While isolates from cats and dogs were spread across the phylogenetic tree, human infections were caused almost exclusively by subsp. strains. Most of the human isolates were capsule type A and LPS type L1 and L3; however, some strains lacked a capsule biosynthesis locus, and some strains contained a novel LPS outer-core locus, distinct from the eight LPS loci that can currently be identified using an LPS multiplex PCR. In addition, the strains isolated from human infections contained novel mobile genetic elements. We compiled a curated database of known virulence factor and antibiotic resistance genes (PastyVRDB) allowing for detailed characterization of isolates. The majority of human isolates encoded a reduced range of iron receptors and contained only one filamentous hemagglutinin gene. Finally, gene-trait analysis identified a putative L-fucose uptake and utilization pathway that was over-represented in subsp. strains and may represent a novel host predilection mechanism in this subspecies. Together, these analyses have identified pathogenic mechanisms likely important for zoonotic infections.IMPORTANCE can cause serious infections in humans, including skin and wound infections, pneumonia, peritonitis, meningitis, and bacteraemia. Cats and dogs are known vectors of human pasteurellosis, transmitting via bite wounds or contact with animal saliva. The mechanisms that underpin human predilection and pathogenesis are poorly understood. With increasing identification of antibiotic-resistant strains, understanding these mechanisms is vital for developing novel treatments and control strategies to combat human infection. Here, we show that a narrow range of strains cause disease in humans, while cats and dogs, common vectors for zoonotic infections, can harbor a wide range of strains. We also present a curated -specific database, allowing quick and detailed characterization of newly sequenced isolates.