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

Jane Turton,Zoë Payne,Frances Davies,Jack Turton,Claire Perry,Rachel Pike

doi:10.3390/microorganisms7090326

Jane Turton, Zoë Payne + Show 4 more

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https://doi.org/10.3390/microorganisms7090326

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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.

Highlights

Klebsiella pneumoniae poses a dual threat to human health; in the community, it is associated with invasive disease, which can affect young, otherwise healthy people, while in the nosocomial setting it has a marked propensity to acquire antibiotic resistance [1,2,3]
“hypervirulence” has been associated only with particular types, such as capsular type K1 sequence type (ST) 23 (K1-ST23) and capsular type K2 ST86 (K2-ST86), which were generally susceptible to antibiotics, but recently, virulence elements found in these types have been described in other STs that are strongly associated with resistance, such as STs 11, 15 and 383 [7,8,9,10]
The high-risk clones described here are not gaining the virulence plasmids found in hypervirulent types, which do not generally contain antibiotic resistance genes, but carry their own versions that combine both resistance and virulence elements

Summary

Introduction

Klebsiella pneumoniae poses a dual threat to human health; in the community, it is associated with invasive disease, which can affect young, otherwise healthy people, while in the nosocomial setting it has a marked propensity to acquire antibiotic resistance [1,2,3]. “hypervirulence” has been associated only with particular types, such as capsular type K1 sequence type (ST) 23 (K1-ST23) and capsular type K2 ST86 (K2-ST86), which were generally susceptible to antibiotics, but recently, virulence elements found in these types have been described in other STs that are strongly associated with resistance, such as STs 11, 15 and 383 [7,8,9,10] Many of these elements are carried on a large virulence plasmid, which typically carries acquired siderophore genes (especially for aerobactin, and for salmochelin and enterochelin), heavy metal resistance genes (coding for tellurite, silver, copper and lead resistance) and capsule up-regulation genes, rmpA and rmpA2. Sequencing of further carbapenemase-gene-positive nosocomial isolates has identified twelve more isolates carrying hybrid resistance/virulence plasmids, three carrying a plasmid containing both blaNDM-5 and virulence genes, which we describe here

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