No 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 yersinibactin (ybtS), aerobactin (iutA) genes. Importantly, 98% of ESBL and 62% of carbapenamasen isolates harboured ybtS, iutA and rmpA, magA respectively. The IncF conjugative plasmids are predominant in K. pneumoniae, which contribute to the spread of AMR, 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.

In recent times K. pneumoniae, a common nosocomial pathogen, tends to evolve more virulent and multidrug-resistant. Urinary tract infections by antibiotic resistant and virulent K. pneumoniae are a growing concern due to the challenging treatment strategies. Hence understanding the genome and validating the genomic profile along with pan-genome analysis will facilitate surveillance of high risk-clones of K. pneumoniae to underpin management strategies toward early detection. Thus, the present study aimed to correlate genotypic and phenotypic antimicrobial resistance and pathogenicity associated with sequence types and virulence factors in Klebsiella spp. The complete genome profile of 3 K. pneumoniae and a K. variicola were analysed in the study which was assigned to ST200, ST45, ST147 and ST of K. variicola are not known. The accessory genome comprised 66% of genes consisting of shell and cloud genes in K. pneumoniae. The phenotypic antimicrobial resistance identified kp3 to have maximum resistance and the susceptibility of environment isolate K. variicola was less resistant to the tested antibiotics. The in vitro and genomic antimicrobial resistance profiling showed concordance with all the tested antibiotics against the 4 study strains. Hypermucoviscosity was not observed for any of the test isolates; this phenotypic character matches perfectly with the absence of rmpA, rmpA2 and magA. Though the genes encoding for major virulence factors; hypermucoviscosity, yersiniabactin and allantoin metabolism were absent, significant pathogenicity and mortality were observed for kp3 isolate in the Zebrafish infection model. In contrast, the isolates predicted with the aerobactin gene were observed with least mortality rate. In the present study virulome and in vivo study illustrate the discrepancies in the virulence. To the best of our knowledge, this is the first report on the presence of ste, stf, stc and sti major fimbrial operons of Salmonella enteric serotype Typhimurium in K. pneumoniae genome, that might contribute to the virulence of kp3. Our study highlights the further necessity of genomic and phenotypic virulence markers for timely diagnosis and immediate treatment for the management of high risk K. pneumoniae clones.

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.

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.