Genome Analyses of A Worldwide Multisource Collection of Klebsiella variicola Reveal Adaptation Relevant for Human Infection

AO_SCPLOWBSTRACTC_SCPLOWKlebsiella variicola (K.var), part of the Klebsiella pneumoniae (K.pne) species complex, is an emerging human pathogen originally associated with plants. Phylogenomic analyses of a global dataset of isolates categorised as human, animal, plant, or environmental strains suggest that K.var are broadly disseminated regardless of hosts or habitats and exhibit genomic variability that is relevant for occupying and transmitting within and across multiple sources. Ancestral state analyses confirm that K.var are originally derived from non-human sources. Genome-wide association analyses of human versus non-human isolates of K.var indicate isolates from human origins are linked to the loss of cold-shock response genes such as lpxP and cspB. Importantly, human K.var isolates also showed enriched antimicrobial resistance gene content and diversity acquired through mobile genetic elements, horizontal gene transfer and mutations within the chromosomal loci which underscore the impact of antimicrobial exposure and proximity to antibiotic resistant K.pne in nosocomial environments. Capsular profiles of K.var suggest high levels of variability in gene composition and indicate that gene functionality for wcaJ in capsule formation differs between K.var and K.pne. Although capsular specialisation was not observed in a host/habitat or lineage-dependent manner, human isolates harbour, on average, a higher siderophore gene content in addition to mrkD mutations which impact on fimbriae and biofilm formation. There is limited evidence of any specific K.var lineages exhibiting convergence of both virulence and antimicrobial resistance genotypes which suggest that these attributes are evolving independently in clinical strains. Our work highlights that gene attrition and acquisition provide a basis for adaptation of K.var as human pathogens. The broad distribution and evolution of K.var highlight the need for improved diagnostic precision and surveillance under a One Health framework.