Molecular characterization of carbapenem-resistant and virulent plasmids in Klebsiella pneumoniae from patients with bloodstream infections in China

Yongqiang Yang; Yanxian Yang; Guanping Chen; Minmin Lin; Yuan Chen; Ruowen He; Klibs N Galvão; Mohamed Abd El-Gawad El-Sayed Ahmed; Adam P Roberts; Yiping Wu; Lan-Lan Zhong; Xiaoxue Liang; Mingyang Qin; Xin Ding; Wenbin Deng; Songyin Huang; Hong-Yu Li; Min Dai; Ding-Qiang Chen; Liyan Zhang; Kang Liao; Yong Xia; Guo-Bao Tian

doi:10.1080/22221751.2021.1906163

Molecular characterization of carbapenem-resistant and virulent plasmids in Klebsiella pneumoniae from patients with bloodstream infections in China

Emerg Microbes Infect. 2021 Dec;10(1):700-709. doi: 10.1080/22221751.2021.1906163.

Authors

Yongqiang Yang^{1

2

3}, Yanxian Yang^{1

2}, Guanping Chen⁴, Minmin Lin⁵, Yuan Chen⁴, Ruowen He^{1

2}, Klibs N Galvão⁶, Mohamed Abd El-Gawad El-Sayed Ahmed^{1

2

7}, Adam P Roberts^{8

9}, Yiping Wu^{1

2}, Lan-Lan Zhong^{1

2}, Xiaoxue Liang¹⁰, Mingyang Qin¹¹, Xin Ding³, Wenbin Deng³, Songyin Huang¹², Hong-Yu Li¹², Min Dai¹⁰, Ding-Qiang Chen¹³, Liyan Zhang¹⁴, Kang Liao¹⁵, Yong Xia¹⁶, Guo-Bao Tian^{1

2

17}

Affiliations

¹ Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
² Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, People's Republic of China.
³ School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou, People's Republic of China.
⁴ Sun Yat-sen University School of Medicine, Guangzhou, People's Republic of China.
⁵ Department of Respiratory Medicine, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People's Republic of China.
⁶ Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
⁷ Department of Microbiology and Immunology, Faculty of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Cairo, Egypt.
⁸ Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Pembroke Place, UK.
⁹ Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine, Pembroke Place, UK.
¹⁰ School of Laboratory Medicine, Chengdu Medical College, Chengdu, People's Republic of China.
¹¹ Basic Medical College, Xinxiang Medical University, Xinxiang, People's Republic of China.
¹² Department of Clinical Laboratory, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
¹³ Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
¹⁴ Department of Clinical Laboratory, Guangdong Provincial People's Hospital / Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
¹⁵ Department of Clinical Laboratory, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People's Republic of China.
¹⁶ Department of Clinical Laboratory Medicine, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
¹⁷ School of Medicine, Xizang Minzu University, Xianyang, People's Republic of China.

Abstract

Bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are potentially life-threatening and an urgent threat to public health. The present study aims to clarify the characteristics of carbapenemase-encoding and virulent plasmids, and their interactions with the host bacterium. A total of 425 Kp isolates were collected from the blood of BSI patients from nine Chinese hospitals, between 2005 and 2019. Integrated epidemiological and genomic data showed that ST11 and ST307 Kp isolates were associated with nosocomial outbreak and transmission. Comparative analysis of 147 Kp genomes and 39 completely assembled chromosomes revealed extensive interruption of acrR by ISKpn26 in all Kp carbapenemase-2 (KPC-2)-producing ST11 Kp isolates, leading to activation of the AcrAB-Tolc multidrug efflux pump and a subsequent reduction in susceptibility to the last-resort antibiotic tigecycline and six other antibiotics. We described 29 KPC-2 plasmids showing diverse structures, two virulence plasmids in two KPC-2-producing Kp, and two novel multidrug-resistant (MDR)-virulent plasmids. This study revealed a multifactorial impact of KPC-2 plasmid on Kp, which may be associated with nosocomial dissemination of MDR isolates.

Keywords: Bloodstream infection; KPC-2; Klebsiella pneumoniae; carbapenem resistance; genomics.

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology*
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
Carbapenems / pharmacology*
China / epidemiology
Drug Resistance, Bacterial
Humans
Klebsiella Infections / epidemiology
Klebsiella Infections / microbiology*
Klebsiella pneumoniae / classification
Klebsiella pneumoniae / drug effects
Klebsiella pneumoniae / isolation & purification*
Klebsiella pneumoniae / pathogenicity
Microbial Sensitivity Tests
Molecular Epidemiology
Moths
Phylogeny
Sepsis / epidemiology
Sepsis / microbiology*
Virulence
beta-Lactamases / genetics
beta-Lactamases / metabolism

Substances

Anti-Bacterial Agents
Bacterial Proteins
Carbapenems
beta-Lactamases
carbapenemase

Grants and funding

This work was funded by the National Natural Science Foundation of China (grant numbers 82061128001, 81722030, 81830103, 81902123), National Key Research and Development Program (grant number 2017ZX10302301), Guangdong Natural Science Foundation (grant number 2017A030306012), Project of high-level health teams of Zhuhai at 2018 (The Innovation Team for Antimicrobial Resistance and Clinical Infection), 111 Project (grant number B12003), Open project of Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education (grant number 2018kfkt01/02), China Postdoctoral Science Foundation (grant number 2019M653192), Science, Technology, and Innovation Commission of Shenzhen Municipality (JCYJ20190807151601699).