Population Structure, Antibiotic Resistance, and Uropathogenicity of Klebsiella variicola

Abstract

<i>Klebsiella variicola</i> is a member of the <i>Klebsiella</i> genus and often misidentified as <i>Klebsiella pneumoniae</i> or <i>Klebsiella quasipneumoniae</i> The importance of <i>K. pneumoniae</i> human infections has been known; however, a dearth of relative knowledge exists for <i>K. variicola</i> Despite its growing clinical importance, comprehensive analyses of <i>K. variicola</i> population structure and mechanistic investigations of virulence factors and antibiotic resistance genes have not yet been performed. To address this, we utilized <i>in silico</i>, <i>in vitro</i>, and <i>in vivo</i> methods to study a cohort of <i>K. variicola</i> isolates and genomes. We found that the <i>K. variicola</i> population structure has two distant lineages composed of two and 143 genomes, respectively. Ten of 145 <i>K. variicola</i> genomes harbored carbapenem resistance genes, and 6/145 contained complete virulence operons. While the β-lactam <i>bla</i>_LEN and quinolone <i>oqxAB</i> antibiotic resistance genes were generally conserved within our institutional cohort, unexpectedly 11 isolates were nonresistant to the β-lactam ampicillin and only one isolate was nonsusceptible to the quinolone ciprofloxacin. <i>K. variicola</i> isolates have variation in ability to cause urinary tract infections in a newly developed murine model, but importantly a strain had statistically significant higher bladder CFU than the model uropathogenic <i>K. pneumoniae</i> strain TOP52. Type 1 pilus and genomic identification of altered <i>fim</i> operon structure were associated with differences in bladder CFU for the tested strains. Nine newly reported types of pilus genes were discovered in the <i>K. variicola</i> pan-genome, including the first identified P-pilus in <i>Klebsiella</i> spp.<b>IMPORTANCE</b> Infections caused by antibiotic-resistant bacterial pathogens are a growing public health threat. Understanding of pathogen relatedness and biology is imperative for tracking outbreaks and developing therapeutics. Here, we detail the phylogenetic structure of 145 <i>K. variicola</i> genomes from different continents. Our results have important clinical ramifications as high-risk antibiotic resistance genes are present in <i>K. variicola</i> genomes from a variety of geographic locations and as we demonstrate that <i>K. variicola</i> clinical isolates can establish higher bladder titers than <i>K. pneumoniae</i> Differential presence of these pilus genes in<i>K. variicola</i> isolates may indicate adaption for specific environmental niches. Therefore, due to the potential of multidrug resistance and pathogenic efficacy, identification of <i>K. variicola</i> and <i>K. pneumoniae</i> to a species level should be performed to optimally improve patient outcomes during infection. This work provides a foundation for our improved understanding of <i>K. variicola</i> biology and pathogenesis.