Detection and molecular characterisation of amikacin-resistant Mycobacterium abscessus isolated from patients with pulmonary disease

Mingyan Wu; Bing Li; Qi Guo; Liyun Xu; Yuzhen Zou; Yongjie Zhang; Mengling Zhan; Benyong Xu; Meiping Ye; Fangyou Yu; Zhemin Zhang; Haiqing Chu

doi:10.1016/j.jgar.2019.05.016

Detection and molecular characterisation of amikacin-resistant Mycobacterium abscessus isolated from patients with pulmonary disease

J Glob Antimicrob Resist. 2019 Dec:19:188-191. doi: 10.1016/j.jgar.2019.05.016. Epub 2019 May 20.

Authors

Mingyan Wu¹, Bing Li², Qi Guo¹, Liyun Xu², Yuzhen Zou¹, Yongjie Zhang¹, Mengling Zhan¹, Benyong Xu¹, Meiping Ye², Fangyou Yu³, Zhemin Zhang⁴, Haiqing Chu⁵

Affiliations

¹ Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Tongji University School of Medicine, Shanghai 200092, China.
² Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
³ Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
⁴ Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: zhemindoc@163.com.
⁵ Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: chu_haiqing@126.com.

PMID: 31121335
DOI: 10.1016/j.jgar.2019.05.016

Abstract

Objectives: The aim of this study was to investigate the molecular mechanisms conferring amikacin (AMK) resistance in Mycobacterium abscessus clinical isolates.

Methods: A total of 194M. abscessus clinical isolates were collected from patients with pulmonary disease during the period 2012-2017. AMK susceptibility was determined by the broth microdilution method. Whole-genome data were used for identification of mutations in resistance-associated genes. Quantitative reverse transcription PCR (qRT-PCR) was performed to measure the gene transcriptional level.

Results: AMK showed high in vitro killing activity against M. abscessus, with an MIC₅₀ of 8mg/L and an MIC₉₀ of 16mg/L. Five isolates (2.6%) were resistant to AMK (MIC>1024mg/L), of which four (80.0%) harboured a resistance-associated rrs mutation A1408G. qRT-PCR analysis showed that most of the AMK-resistant isolates (4/5; 80.0%) overexpressed the transcriptional regulator gene whiB7 and the multidrug-efflux transporter gene tap. However, overexpression of the aminoglycoside-modifying enzyme gene eis2 was only observed in one (20.0%) AMK-resistant isolate.

Conclusion: The AMK resistance rate in M. abscessus clinical isolates in this study was low (2.6%). The A1408G mutation in rrs and overexpression of WhiB7 and Tap were the predominant mechanisms of AMK resistance in M. abscessus.

Keywords: Amikacin; MIC distribution; Mycobacterium abscessus; Resistance mechanism.

Publication types

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

MeSH terms

Amikacin / pharmacology*
Bacterial Proteins / genetics*
Drug Resistance, Bacterial*
Gene Expression Profiling / methods
Gene Expression Regulation, Bacterial
Humans
Lung Diseases / microbiology*
Microbial Sensitivity Tests
Mutation
Mycobacterium abscessus / drug effects
Mycobacterium abscessus / genetics
Mycobacterium abscessus / isolation & purification*
Whole Genome Sequencing

Substances

Bacterial Proteins
Amikacin