TY - JOUR
T1 - Population structure, antibiotic resistance, and uropathogenicity of klebsiella variicola
AU - Potter, Robert F.
AU - Lainhart, William
AU - Twentyman, Joy
AU - Wallace, Meghan A.
AU - Wang, Bin
AU - Burnham, Carey Ann D.
AU - Rosen, David A.
AU - Dantas, Gautam
N1 - Publisher Copyright:
© 2018 Potter et al.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Klebsiella variicola is a member of the Klebsiella genus and often misidentified as Klebsiella pneumoniae or Klebsiella quasipneumoniae. The importance of K. pneumoniae human infections has been known; however, a dearth of relative knowledge exists for K. variicola. Despite its growing clinical importance, comprehensive analyses of K. variicola population structure and mechanistic investigations of virulence factors and antibiotic resistance genes have not yet been performed. To address this, we utilized in silico, in vitro, and in vivo methods to study a cohort of K. variicola isolates and genomes. We found that the K. variicola population structure has two distant lineages composed of two and 143 genomes, respectively. Ten of 145 K. variicola genomes harbored carbapenem resistance genes, and 6/145 contained complete virulence operons. While the β-lactam bla LEN and quinolone oqxAB 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. K. variicola 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 K. pneumoniae strain TOP52. Type 1 pilus and genomic identification of altered fim operon structure were associated with differences in bladder CFU for the tested strains. Nine newly reported types of pilus genes were discovered in the K. variicola pan-genome, including the first identified P-pilus in Klebsiella spp. IMPORTANCE 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 K. variicola genomes from different continents. Our results have important clinical ramifications as high-risk antibiotic resistance genes are present in K. variicola genomes from a variety of geographic locations and as we demonstrate that K. variicola clinical isolates can establish higher bladder titers than K. pneumoniae. Differential presence of these pilus genes in K. variicola isolates may indicate adaption for specific environmental niches. Therefore, due to the potential of multidrug resistance and pathogenic efficacy, identification of K. variicola and K. pneumoniae to a species level should be performed to optimally improve patient outcomes during infection. This work provides a foundation for our improved understanding of K. variicola biology and pathogenesis.
AB - Klebsiella variicola is a member of the Klebsiella genus and often misidentified as Klebsiella pneumoniae or Klebsiella quasipneumoniae. The importance of K. pneumoniae human infections has been known; however, a dearth of relative knowledge exists for K. variicola. Despite its growing clinical importance, comprehensive analyses of K. variicola population structure and mechanistic investigations of virulence factors and antibiotic resistance genes have not yet been performed. To address this, we utilized in silico, in vitro, and in vivo methods to study a cohort of K. variicola isolates and genomes. We found that the K. variicola population structure has two distant lineages composed of two and 143 genomes, respectively. Ten of 145 K. variicola genomes harbored carbapenem resistance genes, and 6/145 contained complete virulence operons. While the β-lactam bla LEN and quinolone oqxAB 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. K. variicola 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 K. pneumoniae strain TOP52. Type 1 pilus and genomic identification of altered fim operon structure were associated with differences in bladder CFU for the tested strains. Nine newly reported types of pilus genes were discovered in the K. variicola pan-genome, including the first identified P-pilus in Klebsiella spp. IMPORTANCE 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 K. variicola genomes from different continents. Our results have important clinical ramifications as high-risk antibiotic resistance genes are present in K. variicola genomes from a variety of geographic locations and as we demonstrate that K. variicola clinical isolates can establish higher bladder titers than K. pneumoniae. Differential presence of these pilus genes in K. variicola isolates may indicate adaption for specific environmental niches. Therefore, due to the potential of multidrug resistance and pathogenic efficacy, identification of K. variicola and K. pneumoniae to a species level should be performed to optimally improve patient outcomes during infection. This work provides a foundation for our improved understanding of K. variicola biology and pathogenesis.
KW - Antibiotic resistance
KW - Emerging pathogens
KW - Klebsiella
KW - Microbial genomics
KW - Urinary tract infection
UR - http://www.scopus.com/inward/record.url?scp=85058883678&partnerID=8YFLogxK
U2 - 10.1128/mBio.02481-18
DO - 10.1128/mBio.02481-18
M3 - Article
C2 - 30563902
AN - SCOPUS:85058883678
SN - 2161-2129
VL - 9
JO - mBio
JF - mBio
IS - 6
M1 - e02481-18
ER -