Hybrid Resistance and Virulence Plasmids in “High-Risk” Clones of Klebsiella pneumoniae, Including Those Carrying blaNDM-5

Abstract

Virulence plasmids are associated with hypervirulent types of Klebsiella pneumoniae, which generally do not carry antibiotic resistance genes. In contrast, nosocomial isolates are often associated with resistance, but rarely with virulence plasmids. Here, we describe virulence plasmids in nosocomial isolates of “high-risk” clones of sequence types (STs) 15, 48, 101, 147 and 383 carrying carbapenemase genes. The whole genome sequences were determined by long-read nanopore sequencing. The 12 isolates all contained hybrid plasmids containing both resistance and virulence genes. All carried rmpA/rmpA2 and the aerobactin cluster, with the virulence plasmids of two of three representatives of ST383 carrying blaNDM-5 and seventeen other resistance genes. Representatives of ST48 and ST15 had virulence plasmid-associated genes distributed between two plasmids, both containing antibiotic resistance genes. Representatives of ST101 were remarkable in all sharing virulence plasmids in which iucC and terAWXYZ were missing and iucB and iucD truncated. The combination of resistance and virulence in plasmids of high-risk clones is extremely worrying. Virulence plasmids were often notably consistent within a lineage, even in the absence of epidemiological links, suggesting they are not moving between types. However, there was a common segment containing multiple resistance genes in virulence plasmids of representatives of both STs 48 and 383.

Emergence of New Non–Clonal Group 258 High-Risk Clones among Klebsiella pneumoniae Carbapenemase–Producing K. pneumoniae Isolates, France

“…In addition, our study highlights the dissemination of bla KPC genes in high-risk clones of K. pneumoniae (ST307 and ST147), genetic features that might provide an advantage in adaptation to the hospital environment and the human host (39). These clones already convey several antimicrobial-resistance genes, including genes encoding other carbapenemases of NDM and OXA-48-like types (40,41). Accordingly, we might now fear the emergence of ST307 and ST147 high-risk clones of K. pneumoniae that can co-produce multiple carbapenemases.…”

A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition

“…The fact that these key hypervirulence features in addition to disinfectant resistance are found on mutual virulence/resistance plasmids in extensively drug-resistant isolates is concerning and has tremendous public health implications as these mobile genetic elements may be transferred across different bacteria [75]. Our previous work, and those of others, suggests that the combination of high-level drug resistance and virulence is a good combination for the successful spread of bacterial pathogens [3,53,[76][77][78][79]. On the other hand, the co-carriage of plasmid-encoded heavy metal efflux genes did not significantly impact the phenotypic tolerance in the study's K. pneumoniae outbreak isolates, pointing towards that this capacity is less likely a major contributor to the clone's success in this outbreak situation.…”

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from South and Southeast Asia

“…This is consistent with their local dissemination or recent acquisition from a common source, a finding supported by the discovery of four novel but similar iuc3 encoding plasmids in these isolates. Of greatest concern was the detection of at least nine distinct convergence events between AMR and hypervirulence (encompassing 7·3% of isolates) plus seven novel dual AMR + iuc containing plasmids, increasing the total number of convergent plasmids reported so far by almost 50% [49,[80][81][82][83]. Given that our isolate collection represented a snapshot from seven diagnostic laboratories, we predict that many additional convergent plasmid variants await future identification.…”