Research Article: Whole genome sequencing for drug resistance determination in Mycobacterium tuberculosis

Date Published: February 21, 2019

Publisher: AOSIS

Author(s): Shaheed V. Omar, Lavania Joseph, Halima M. Said, Farzana Ismail, Nabila Ismail, Thabisile L. Gwala, Nazir A. Ismail.


South Africa remains challenged with a high tuberculosis burden accompanied by an increase in drug resistant cases. We assessed the use of the Illumina MiSeq, a next-generation sequencing platform for whole genome sequencing, followed by bioinformatic analysis using a commercial software package to determine resistance to selected drugs used for Mycobacterium tuberculosis treatment in our setting. Whole genome sequencing shows potential as a diagnostic platform for the detection of drug resistance in Mycobacterium tuberculosis with the provision of information for several drugs simultaneously.

Partial Text

Drug-resistant tuberculosis poses a significant challenge to tuberculosis control programmes in high burden settings.1 Undiagnosed drug resistance leads to further transmission, poor patient outcomes and potential for amplification of drug resistance, impeding the World Health Organization’s (WHO) strategy to end tuberculosis by 2035. The drug-resistant tuberculosis outbreaks in Tugela Ferry2 and other regions of South Africa3 highlight the need for early and accurate diagnosis of drug resistance.

Concordance between WGS and the phenotypic DST method for resistance determination was noted for all isolates except one phenotypically susceptible isolate for all targets explored (Table 1 and Table 2). The phenotypically susceptible isolate harboured a known resistance associated mutation in the fabG1/mabA (inhA promoter) region (inhA promoter c-15t) detected by WGS. This finding was confirmed by the MTBDRplus assay displaying an inhAmut1 mutation, and resistance was confirmed by the broth microdilution assay (minimum inhibitory concentration of 0.25 µg/ml) (Table 2). Interestingly, we found that a multidrug resistant isolate was incorrectly classified as susceptible to rifampicin by the MTBDRplus assay and resistant by both MGIT DST and WGS; the latter detected the presence of the rpoBL511P mutation, a known rifampicin resistance determinant.

The application of whole genome next-generation sequencing technology for drug resistance determination in M. tuberculosis has been shown to be a valuable tool in this study. Despite the small sample size, the performance of WGS for predicting resistance was consistent with published studies containing subsets of South African isolates.25,26




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