Mutations in MDR-TB Isolates from Bedaquiline-Resistance Conferring Mulago Hospital Kampala, Uganda

Abstract

Introduction: In 2018, based on an evidence-based policy, the World Health Organization (WHO) updated its guidelines on the treatment of drug-resistant tuberculosis with recommendation of bedaquiline as a core drug in the standard combination regimen for the treatment of rifampin-resistant TB. Bedaquiline, a new anti-tuberculosis drug, has already been used in greater than 50 countries. Resistance to BDQ was previously shown to be due to non-target and target-based mutations (Rv0678 and atpE genes) respectively. While bedaquiline (BDQ) was recently approved as a new ant TB drug in patients with multidrug and extensively resistant TB, there is insufficient baseline data on the type and burden of mutations conferring resistance to this drug among the MTB isolates from Mulago TB ward patients. Aim: Here, we describe the prevalence and patterns of bedaquiline resistance conferring mutations in isolates collected from patents attending Mulago TB ward. Significance: Generated bedaquiline resistance conferring mutations baseline data may be a potential to which surveillances could be done. Methods: Baseline MDR-TB isolates from patients at Mulago TB ward were cultured on 7H10. Chromosomal DNA was extracted and amplify the target on PCR with atpE specific primers. PCR and DNA sequencing was done by Sanger method to identify mutations in the same gene. Generated sequences were analysed using BioEdit v7.2.5.0. Results: One mutation 1/51 (1.96%) was identified showing Tyr19 to His and no mutation was observed in the 50 baseline MDR –TB isolates. Conclusion Mutations in atpE gene occur in MDR-TB isolates without prior use of bedaquiline. The results obtained from our study is promising and should help facilitate routine genotypic drug susceptibility testing for bedaquiline and stimulate further research to help avoid the emergence of resistance to this new treatment through early detection.