A Small KPC-2-Producing Plasmid in Klebsiella pneumoniae: Implications for Diversified Vehicles of Carbapenem Resistance

Qiwei Chen; Lizhang Liu; Xiaofang Hu; Xu Jia; Xiaowei Gong; Youjun Feng; Man Huang

doi:10.1128/spectrum.02688-21

A Small KPC-2-Producing Plasmid in Klebsiella pneumoniae: Implications for Diversified Vehicles of Carbapenem Resistance

Microbiol Spectr. 2022 Jun 29;10(3):e0268821. doi: 10.1128/spectrum.02688-21. Epub 2022 May 17.

Authors

Qiwei Chen^#^{1

2

3}, Lizhang Liu^#^{2

3}, Xiaofang Hu^{2

4}, Xu Jia⁵, Xiaowei Gong^{1

2

3}, Youjun Feng^{2

3

5

6}, Man Huang^{2

3}

Affiliations

¹ State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.
² Department of Microbiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
³ General Intensive Care Unit of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
⁴ Fuzhou Medical College of Nanchang University, Fuzhou, Jiangxi, China.
⁵ Non-coding RNA and Drug Discovery Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, Sichuan, China.
⁶ College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, China.

^# Contributed equally.

Abstract

The convergence of hypervirulence to carbapenem-resistant K. pneumoniae (CRKP) in a highly transmissible ST11 clone poses a great challenge to public health and anti-infection therapy. Recently, we revealed that an expanding repertoire of diversified KPC-2-producing plasmids occurs in these high-risk clones. Here, we report a clinical case infected with a rare isolate of ST437 CRKP, K186, which exhibited KPC-2 production. Apart from its 5,322,657-bp long chromosome, whole-genome sequencing of strain K186 elucidated three distinct resistance plasmids (designated pK186_1, pK186_2, and pK186_KPC, respectively). Unlike the prevalently larger form of KPC-2-producing plasmids (~120 to ~170 kb) earlier we observed, pK186_KPC is an IncN-type, small plasmid of 26,012bp in length. Combined with the colinear alignment of plasmid genome, the analyses of insertion sequences further suggested that this carbapenem-resistant pK186_KPC might arise from the cointegration of its ancestral IncN and IncFII plasmids, exclusively relying on IS26-based transposition events. Taken together, the result represents an unusual example of bla_KPC-2-bearing small plasmids, and highlights an ongoing arsenal of diversified carriers benefiting the transferability of KPC-2 carbapenem resistance. IMPORTANCE A rare ST437 isolate termed K186 was clinically determined which was unlike ST11, the dominant sequence type of CRKP. Whole-genome sequencing enabled us to discover three distinct resistance plasmids, namely, pK186_1, pK186_2, and pK186_KPC. Among them, pK186_KPC appears as a unique plasmid ~26 kb in size, much smaller than the prevalent forms (~120 to ~170 kb). Intriguingly, genetic analysis suggests that it might originate from Proteus mirabilis. This result constitutes an additional example of differentiated plasmid vehicles dedicated to the emergence and dissemination of KPC-2 carbapenem resistance.

Keywords: K. pneumoniae carbapenemase-2; Klebsiella pneumoniae; carbapenem resistance; carbapenem-resistant K. pneumoniae; pK186_KPC; small plasmid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / pharmacology
Bacterial Proteins / genetics
Carbapenems / pharmacology
Humans
Klebsiella Infections*
Klebsiella pneumoniae* / genetics
Microbial Sensitivity Tests
Plasmids / genetics
beta-Lactamases / genetics

Substances

Anti-Bacterial Agents
Bacterial Proteins
Carbapenems
beta-Lactamases