Metagenomics next-generation sequencing (mNGS) reveals emerging infection induced by Klebsiella pneumoniaeniae

Shuang Wan; Aiping Zhou; Rongrong Chen; Shiqi Fang; Jinfeng Lu; Na Lv; Chu Wang; Jianpeng Gao; Jun Li; Wenjuan Wu

doi:10.1016/j.ijantimicag.2023.107056

Metagenomics next-generation sequencing (mNGS) reveals emerging infection induced by Klebsiella pneumoniaeniae

Int J Antimicrob Agents. 2024 Feb;63(2):107056. doi: 10.1016/j.ijantimicag.2023.107056. Epub 2023 Dec 9.

Authors

Shuang Wan¹, Aiping Zhou², Rongrong Chen³, Shiqi Fang⁴, Jinfeng Lu⁴, Na Lv⁴, Chu Wang⁵, Jianpeng Gao⁵, Jun Li⁶, Wenjuan Wu⁷

Affiliations

¹ Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China; College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang, 330045, China.
² Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China; Shanghai East Hospital Ji'an Hospital, Ji'an, 343000, China.
³ College of Bioscience and Bioengineering, Jiangxi Agricultural University, Nanchang, 330045, China.
⁴ College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang, 330045, China.
⁵ Genskey Medical Technology Co., Ltd., Beijing, 102206, China.
⁶ College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang, 330045, China. Electronic address: lijunbioinfo@163.com.
⁷ Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China. Electronic address: wwj1210@126.com.

PMID: 38081548
DOI: 10.1016/j.ijantimicag.2023.107056

Abstract

Objectives: The increasing emergence of hypervirulent Klebsiella pneumoniae (hv-Kp) and carbapenem-resistant K. pneumoniae (CR-Kp) is a serious and substantial public health problem. The use of the last resort antimicrobials, tigecycline and polymyxin to combat infections is complicated by the expanding repertoire of newly-identified CR-hvKp. The transmission and co-occurrence of the corresponding antimicrobial resistance and virulence determinants are largely unknown. The aim of this study was to investigate the dissemination and dynamics of CR-Kp and its antibiotic resistance in a hospitalised patient.

Methods: Metagenomic next-generation sequencing (mNGS) was conducted for different specimens collected from an elderly male hospitalised patient. CR-Kp strains were examined using antibiotic susceptibility and string testing. Antimicrobial and virulence genes were annotated using whole-genome sequencing (WGS).

Results: A clinical case of a patient infected with a variety of CR-Kp isolates was reported. The co-occurrence of KPC-2 and NDM-1 in the patient was revealed. The CR-Kp isolates, such as BALF2, and Sputum T1 and T3, were classified into ST11 and ST147, respectively. The genetic signature (iuc operon) of hypervirulence was identified in strain T1, although string testing indicated its intermediate virulence.

Conclusions: In this study, multiple infections of CR-Kp isolates were revealed by mNGS, and their dissemination was attributed to plasmid variations, mgrB inactivation and integrative conjugative elements (ICEs). Furthermore, the finding indicated one likely convergence to form CR-hvKp, different from acquisition of carbapenem-resistance determinants in hvKp. A combination of mNGS and WGS is beneficial for clinical diagnosis and anti-infection therapy, and facilitates a better understanding of genetic variants conferring antimicrobial and virulence properties.

Keywords: Carbapenem and polymyxin resistance; Horizontal gene transfer; Klebsiella pneumoniae; Metagenome sequencing.

Publication types

Case Reports

MeSH terms

Aged
Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Carbapenems / pharmacology
Carbapenems / therapeutic use
High-Throughput Nucleotide Sequencing
Humans
Klebsiella Infections* / drug therapy
Klebsiella pneumoniae
Klebsiella*
Male

Substances

Carbapenems
Anti-Bacterial Agents