Detection and molecular characterisation of amikacin-resistant Mycobacterium abscessus isolated from patients with pulmonary disease. (December 2019)

• Record Type: Journal Article
• Authors: Wu, Mingyan; Li, Bing; Guo, Qi; Xu, Liyun; Zou, Yuzhen; Zhang, Yongjie; Zhan, Mengling; Xu, Benyong; Ye, Meiping; Yu, Fangyou; Zhang, Zhemin; Chu, Haiqing
• Is Part Of: Journal of global antimicrobial resistance. Volume 19(2019)
• Page Start: 188
• Page End: 191
• Publication Date: 2019-12
• Subjects: Mycobacterium abscessus -- Amikacin -- MIC distribution -- Resistance mechanism; Drug resistance -- Periodicals; Drug resistance -- Periodicals; Drug resistance; Periodicals; 616.9041
• DOI: 10.1016/j.jgar.2019.05.016
• Languages: English
• ISSNs: 2213-7165

Abstract

Highlights: Amikacin (AMK) resistance in clinical Mycobacterium abscessus has emerged. Data on the prevalence of AMK resistance and underlying resistance mechanisms in clinical M. abscessus are limited. AMK had high in vitro killing activity against M. abscessus from lung infections, with a resistance rate of 2.6% (5/194). Most of the AMK-resistant isolates harboured a target site rrs mutation. A1408G mutation in rrs and overexpression of WhiB7 and Tap are main mechanisms of AMK resistance in clinical M. abscessus . 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 194 M. 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 8 mg/L and an MIC90 of 16 mg/L. Five isolates (2.6%) were resistant to AMK (MIC > 1024 mg/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 A1408 G mutation in rrs and overexpression of WhiB7 and Tap were the predominant mechanisms of AMK resistance in M. abscessus .