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Indian Journal of Pure & Applied Biosciences (IJPAB)
Year : 2023, Volume : 11, Issue : 2
First page : (1) Last page : (12)
Article doi: : http://dx.doi.org/10.18782/2582-2845.8983

Analysing the Impact of Bedaquiline Resistance in Fluoroquinolone-Resistant Clinical Isolates and Investigating the Molecular Interactions of BDQ with the atpE Gene

Vijayalakshmi Jawaharlal Nehru¹, Muthuraj Muthaiah², Maria Jose Vadakunnel³, Usharani Brammacharry^4*, Sriram Kumar⁵, Shoba Gunasekaran^6
1,3,4Dept. of Genetics, Dr. A.L.M PG Institute of Basic Medical Science, University of Madras, Chennai- 600113, India
²Intermediate Reference Laboratory, State TB Training and Demonstration Centre, Puducherry- 605006, India
³Dept. of Microbiology & Biotechnology, Hindustan College of Arts and Science, Chennai- 603 103, India
⁴Department of Biotechnology, Dwaraka Doss Goverdhan Doss Vaishnav College, Chennai-600106, India
*Corresponding Author E-mail: usharani.unom@gmail.com
Received: 8.01.2023 | Revised: 26.02.2023 | Accepted: 12.03.2023 

 ABSTRACT

The progress of the tuberculosis eradication programme is hindered by the global health issue of drug-resistant tuberculosis, which is a significant threat to the population. Resistance-associated mutations vary geographically, so investigate the prevalence of resistance to fluoroquinolone (anti-TB) drugs and its association with resistance-related mutations in clinical isolates of Tamilnadu (north zone) and Puducherry was carried out. And the resultant fluoroquinolone drug-resistant tuberculosis strains will be subjected to the molecular analysis of bedaquiline resistance to study the mutation in the atpE gene. The study includes 430 specimens received at Intermediate Reference Laboratory, State TB training and Demonstration Centre in the Government Hospital for Chest Diseases for Molecular testing between January 2020 and December 2021. Samples were analysed by GenoType MTBDRslV.2 for the molecular detection of mutations in the gyrA and gyrB genes. FQ resistance was observed in 32 samples (7.4%), most of which were naïve and previous treatment failure cases. Twenty-five isolates had mutations in DNA gyrase subunit -A (gyrA), while mutations in gyrB were observed in only 7 isolates. Mutational analysis revealed that the mutations mainly alter codon 94 (replacing aspartic acid with glycine, D94G), and 90 (replacing alanine with valine, A90V). In Isoniazid Resistance, MDR, and treatment failure cases, the resistance to Fluoroquinolones was most commonly associated with the D94G mutation. A molecular stimulation study evaluates the effect of BDQ on atpE gene by docking, using AutoDock 4.2, showing hydrogen, hydrophobic and electrostatic interactions.

Keywords: Mycobacterium Tuberculosis, Molecular Docking, gyrA, Fluoroquinolones, Bedaquiline.

Full Text : PDF; Journal doi : http://dx.doi.org/10.18782

Cite this article: Nehru, V. J., Muthaiah, M., Vadakunnel, M. J., Brammacharry, U., Kumar, S., & Gunasekaran, S. (2023). Analysing the Impact of Bedaquiline Resistance in fluoroquinolone-Resistant Clinical Isolates and Investigating the Molecular Interactions of BDQ with the atpE Gene, Ind. J. Pure App. Biosci.11(2), 1-12. doi: http://dx.doi.org/10.18782/2582-2845.8983