Genome sequencing of Mycobacterium tuberculosis clinical isolates revealed isoniazid resistance mechanisms undetected by conventional molecular methods.

Details

Serval ID
serval:BIB_81020030909E
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Genome sequencing of Mycobacterium tuberculosis clinical isolates revealed isoniazid resistance mechanisms undetected by conventional molecular methods.
Journal
International journal of antimicrobial agents
Author(s)
Laurent S., Zakham F., Bertelli C., Merz L., Nicod L., Mazza-Stalder J., Greub G., Jaton K., Opota O.
ISSN
1872-7913 (Electronic)
ISSN-L
0924-8579
Publication state
Published
Issued date
08/2020
Peer-reviewed
Oui
Volume
56
Number
2
Pages
106068
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
A combination of targeted molecular methods and phenotypic drug-susceptibility testing is the most widely used approach to detect drug resistance in Mycobacterium tuberculosis isolates. We report the delay in the introduction of an efficient anti-tuberculous drug regimen because of a M. tuberculosis strain displaying a high level of resistance to isoniazid, in the absence of the common mutations associated with isoniazid-resistance, including katG mutations and inhA promoter mutations. Whole-genome sequencing (WGS) identified a large loss-of-function insertion (>1000 pb) at the end of katG in the isolate together with a -57C>T ahpC mutation, a resistance mechanism that would have remained undetected by a conventional molecular targeted approach. A retrospective search using publicly available WGS data of more than 1200 isoniazid-resistant isolates and a similar sized control dataset of isoniazid-susceptible isolates revealed that most (22/31) isoniazid-resistant, KatG loss-of-function mutants had an associated rare ahpC promoter mutation. In contrast, only 7 of 1411 isoniazid-susceptible strains carried a rare ahpC promoter mutation, including shared mutations with the 31 isoniazid-resistant KatG loss-of-function mutants. These results indicate that rare ahpC promoter mutations could be used as a proxy for investigating simultaneous KatG loss-of-function or missense mutations. In addition, WGS in routine diagnosis would improve drug susceptibility testing in M. tuberculosis clinical isolates and is an efficient tool for detecting resistance mechanisms undetected by conventional molecular methods.
Keywords
Isoniazid, Mycobacterium tuberculosis, Resistance, Whole genome sequencing, ahpC, katG, IS6110, MDR-TB, PCR, isoniazid, isoniazid mono-resistance, isoniazid-resistance, molecular diagnostic, resistance, whole-genome sequencing
Pubmed
Web of science
Open Access
Yes
Create date
03/07/2020 17:03
Last modification date
29/01/2021 7:25
Usage data