Pathogenomic analysis and characterization ofstrains recovered from human infections.

Abstract

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 ofisolates recovered from a range of human infections, from the mouths of cats, and from wounds on dogs. Together with publicly availablegenome 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, thestrains isolated from human infections contained novel mobile genetic elements. We compiled a curated database of knownvirulence factor and antibiotic resistance genes (PastyVRDB) allowing for detailed characterization of isolates. The majority of humanisolates 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 forzoonotic infections.IMPORTANCEcan cause serious infections in humans, including skin and wound infections, pneumonia, peritonitis, meningitis, and bacteraemia. Cats and dogs are known vectors of human pasteurellosis, transmittingvia bite wounds or contact with animal saliva. The mechanisms that underpinhuman predilection and pathogenesis are poorly understood. With increasing identification of antibiotic-resistantstrains, understanding these mechanisms is vital for developing novel treatments and control strategies to combathuman infection. Here, we show that a narrow range ofstrains cause disease in humans, while cats and dogs, common vectors for zoonotic infections, can harbor a wide range ofstrains. We also present a curated-specific database, allowing quick and detailed characterization of newly sequencedisolates.