Coexistence Of Plasmid-Mediated mcr-1 And bla NDM-4 Genes In A Klebsiella pneumoniae Clinical Strain In Vietnam

Lien Le; Linh Khanh Tran; Tam-Duong Le-Ha; Bich-Phuong Tran; Hong-Ngoc Le-Vo; Yen-Nhi Nguyen; Hanh-Lan Nguyen; Khanh-Quynh Hoang-Ngoc; Yuki Matsumoto; Daisuke Motooka; Shota Nakamura; James W Jones; Tetsuya Iida; Van Cao

doi:10.2147/IDR.S226612

Coexistence Of Plasmid-Mediated mcr-1 And bla _NDM-4 Genes In A Klebsiella pneumoniae Clinical Strain In Vietnam

Infect Drug Resist. 2019 Nov 27:12:3703-3707. doi: 10.2147/IDR.S226612. eCollection 2019.

Authors

Affiliations

¹ Department of Immunology and Microbiology, Pasteur Institute in Ho Chi Minh City, Ho Chi Minh City, Vietnam.
² Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
³ Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
⁴ Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

^# Contributed equally.

Abstract

In this study, we characterized the first clinical Klebsiella pneumoniae strain co- harboring mcr-1 and bla _NDM-4 genes in Vietnam, which was recovered from a patient admitted to hospital in 2015. This strain demonstrated nonsusceptible to all tested antibiotics, including last-line antibiotics such as carbapenems (MICs ≥128 μg/mL) and colistin (MIC =32 μg/mL), except tigecycline (MIC =1 μg/mL). Whole-genome analysis using both MinION and MiSeq data revealed that the strain carried 29 resistance genes. Particularly, mcr-1 and bla _NDM-4 genes were carried by different self-conjugative plasmids and able to be transferred to a recipient by conjugation. The colistin resistance of this strain was conferred by mcr-1 and additional chromosomal resistance determinants. Eight amino acid substitutions found in PmrA, PmrB, PmrC, PmrI, and PmrJ, all proteins that are involved in lipopolysaccharide modifications, may be associated with chromosomal colistin resistance. The accumulation of multiple antibiotic resistance mechanisms in this clinical isolate raises alarm on potential spread of extensively drug-resistant K. pneumoniae in healthcare settings.

Keywords: Klebsiella pneumoniae; Vietnam; blaNDM-4; coexistence; mcr-1.

Grants and funding

This work was initially funded by the US Armed Forces Research Institute of Medical Sciences (AFRIMS). Whole genome sequencing of the isolate was supported by the Grant for Joint Research Project of the Research Institute for Microbial Diseases, Osaka University.