Association of Sequence types, Antimicrobial Resistance and Virulence Genes in India isolates of Klebsiella pneumoniae: A Comparative Genomics Study

Abstract

Klebsiella pneumoniae is an important ESKAPE pathogen that causes sepsis, urinary tract infections, peritonitis, intraabdominal abscesses and upper respiratory infections. The strains exhibiting multidrug resistance and hypervirulence are priority pathogens for which immediate treatment and dissemination prevention strategies are required. The hypervirulent drug resistant K. pneumoniae is associated with high mortality rates. Numbers of environmental strains also have acquired virulence genes. Hence to gain a better understanding of the spread of antimicrobial resistant genes across the country over 10 years and to delineate environmental and clinical K. pneumoniae, a comparative genomics investigation was made. This is the first comparative genomic study using India isolates of K. pneumoniae, which includes publicly available WGS of 144 clinical and 9 environmental strains collected during 2010–2020. The blaCTX-M-15 was widely distributed in clinical isolates since 2013 and increased over time from 5 % to 30 %. The co-existence of blaNDM and blaOXA was observed in 22 % of clinical strains. Diverse serotypes were found among the 153 K. pneumoniae isolates, of which, K51 (28%) and K64 (21.56%) were majorly found. Most of the K51 isolates belong to ST231 (93.02 %). And more than 50% of KL51 strains were found to have both rmpA and magA. The number of associated virulence genes (rmpA, magA, entB, ybtS, iutA, alls,) appeared to be higher in ST231-KL51 and ST23-KL1 isolates. Of greatest concern, these virulence genes are observed in environmental strains aswell. More than 97% of clinical strains have ybtS, iutA genes. Importantly, 98% of ESBL and 62% of carbapenamase isolates harbored ybtS, iutA and rmpA, magA respectively. The IncF conjugative plasmids are predominant in K. pneumoniae, which contribute to the spread of antimicrobial resistant and virulence genes. The increasing trend in hypervirulent strains was observed from 2017. The phylogenetic analysis separates the environmental from clinical strains and is characterized by uncommon STs and serotypes. Thus, the study illustrates the K. pneumoniae genomic surveillance in India representing the phylogenetic evolution, STs, AMR, virulence, serotype to provide more attention for immediate treatment and preventing the dissemination of K. pneumoniae.