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.
Highlights
Over the last two decades, the prevalence of colistin resistance among the members of Enterobacteriaceae has been increasing, among Klebsiella pneumoniae isolates; this limits the potential use of colistin and leads to worsened clinical outcomes
Despite the relatively low overall prevalence rate (0.7%, 8/1,171) of mcr-like genes in clinical K. pneumoniae isolates, the presence of mcr (15.1%, 8/53) among the colistin-resistant K. pneumoniae (COLR-KP) isolates indicated that this gene was already widely disseminated among K. pneumoniae isolates in our hospital
All patients had a history of previous hospitalization but without exposure to colistin, none had a history of recent overseas travel
Summary
Over the last two decades, the prevalence of colistin resistance among the members of Enterobacteriaceae has been increasing, among Klebsiella pneumoniae isolates; this limits the potential use of colistin and leads to worsened clinical outcomes. Mutations in genes encoding PhoP/PhoQ and PmrA/PmrB twocomponent regulatory systems regulate the expression of pmrC and pmrHFIJKLM operons and are responsible for the synthesis and transfer of 4-amino-4-deoxy-L-arabinose (L-Ara4N) cationic groups to lipid A This modification increases the positive charge on lipopolysaccharides (LPSs) and decreases colistin binding, leading to colistin resistance (Poirel et al, 2017). All MCR proteins are characterized as phosphoethanolamine (PEtN) transferases They catalyze the attachment of PEtN to lipid A and lead to a reduction of the negative charge of LPS through structural alterations of lipid A and a decrease in the binding of colistin, resulting in colistin resistance (Sun et al, 2018). Several studies have elucidated colistin-resistance mechanisms from different aspects, the underlying mechanism of colistin resistance in clinical K. pneumoniae isolates in our hospital was unclear
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