Molecular Mechanisms of Colistin Resistance in Klebsiella pneumoniae in a Tertiary Care Teaching Hospital

Abstract

BackgroundOver the last two decades, the prevalence of colistin resistance among the members of Enterobacteriaceae has been increasing, particularly among Klebsiella pneumoniae isolates; this limits the potential use of colistin and leads to worsened clinical outcomes.MethodsWe investigated the prevalence and genetic characteristics of colistin-resistant K. pneumoniae (COLR-KP) in clinical isolates using genomic sequencing.ResultsIn total, 53 K. pneumoniae isolates (4.5%, 53/1,171) were confirmed as COLR-KP, of which eight isolates carried mobile colistin-resistant (mcr) gene. Although the overall prevalence rate (0.7%, 8/1,171) of mcr-like genes in clinical K. pneumoniae remained relatively low, the presence of mcr (15.1%, 8/53) among the COLR-KP isolates indicated that the mobile resistance gene was already widespread among K. pneumoniae isolates in hospital setting. We randomly selected 13 COLR-KP isolates (four mcr-bearing and nine non-mcr-bearing isolates) for whole-genome sequencing, including two pandrug-resistant and four sequence type 11 (ST11) isolates. Phylogenetic analysis revealed that all COLR-KP isolates were genetically diverse. Among the four mcr-bearing isolates, three (KP4, KP18, and KP30) were positive for mcr-1 and one (KP23) for mcr-8; none of the other mcr genes were detected. The mcr-1 in the KP4 and KP30 isolates were located in an IncX4 plasmid (approximately 33 kb) and could be successfully transferred to Escherichia coli J53AZR. In contrast, for the mcr-8-bearing plasmid in KP23 (IncFII), colistin resistance could not be transferred by conjugation. The mcr-1-producing isolate KP18 coexists a novel plasmid-carried tigecycline resistance gene tmexCD1-toprJ1. The most common chromosomal mutation associated with colistin resistance was a T246A amino acid substitution in PmrB, which was identified in most COLR-KP isolates (11/13, 84.6%). All ST11 isolates additionally had an R256G amino acid substitution. Critical virulence factors associated with hypervirulent K. pneumoniae were detected in four COLR-KP isolates; these virulence factors included aerobactin, salmochelin, and yersiniabactin.ConclusionWe found that mcr-bearing COLR-KP emerged in our hospital and was growing at an increasing rate. Simultaneous emergence of hypervirulence and colistin–tigecycline–carbapenem resistance in the epidemic clone ST11 K. pneumoniae was also observed; this highlights the significance of active and continuous surveillance.

Prevalence and antimicrobial susceptibility profiles of ESBL-producing Klebsiella Pneumoniae from broiler chicken farms in Shandong Province, China

“…The global spread of ESBL-producing bacteria, especially ESBL-positive E. coli and K. pneumoniae , poses a challenge to treating MDR bacteria ( Chong et al, 2018 ). The resistance of bacteria to colistin in peptide drugs has gradually gained attention as a result of greater attention to carbapenem-resistant K. pneumoniae ( CRKP ), and the emergence of the Mobile Colistin Resistance ( mcr ) gene poses no small threat to global public health ( Wang et al., 2017a ; Liu et al., 2021 ).…”

Analysis of diverse β-lactamases presenting high-level resistance in association with OmpK35 and OmpK36 porins in ESBL-producing Klebsiella pneumoniae

“…The lowest resistance rates were observed against colistin and tigecycline, agreeing with a prior study from Brazil ( Vivan et al, 2017 ). However, emerging colistin resistance has been reported from China ( Liu et al, 2021 ). An extensive spectrum of drug resistance has been observed in OmpK35- and OmpK36-deficient K. pneumoniae , in association with ESBL and AmpC production, leading to the development of substantial resistance against the β-lactam antibiotics, fluoroquinolone, and aminoglycosides ( Hamzaoui et al, 2018 ).…”

Emergence of high-level colistin resistance mediated by multiple determinants, including mcr-1.1, mcr-8.2 and crrB mutations, combined with tigecycline resistance in an ST656 Klebsiella pneumoniae

“…Thus, treatment options for XDR-KP mainly rely on the last-resort antibiotics colistin and tigecycline. However, K. pneumoniae may develop a succession of resistance-associated determinants, including related chromosomal-located mutations or acquired plasmid-mediated resistance genes ( Liu et al., 2021 ).…”

“…The underlying mechanisms contributing to colistin resistance in XDR-KP are usually mediated by chromosomal mutations ( mgrB , phoP / phoQ , pmrA / pmrB and crrAB ) as well as plasmid-related mcr-1 and its variants ( mcr-2 to mcr-10 ) ( Liu et al., 2016 ; Jayol et al., 2017 ; Poirel et al., 2017 ; Wang et al., 2018 ). Nonetheless, the co-existence of mcr-1 and mcr-8 in XDR-KP is relatively rare ( Liu et al., 2021 ).…”