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Bedaquiline Resistance: A Looming Global Threat in Tuberculosis Management

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The development of bedaquiline holds promise for treating multidrug-resistant tuberculosis (MDR-TB). Still, the inflation in bedaquiline resistance has alarmed the global public health crisis, indicating the need for a new treatment strategy. Several scientific studies have reported a high incidence of resistance among MDR-TB patients who had prior exposure to bedaquiline for treating Mycobacterium tuberculosis infections. Disparate research findings indicate that individuals previously administered this drug exhibit a remarkable prevalence of resistance. Studies have further demonstrated that prior treatment often correlates with the emergence of resistant Mycobacterium tuberculosis strains. Overall, evidence from multiple investigations highlights a concerning trend of increased resistance in MDR-TB cases with a history of bedaquiline therapy. Moreover, bedaquiline resistance in MDR-TB strains has been linked to mutations in several chromosomal genes, including atpE, Rv0677c, Rv0678, and pepQ. Consequently, it is imperative to mitigate the burden of MDR-TB and bedaquiline resistance. Herein, this article emphasizes structural features, mechanism of action, emergence of underlying resistance mechanisms, pharmacokinetic & pharmacodynamic properties, clinical toxicity, and strategies to combat resistance associated with bedaquiline.

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Acknowledgements

We acknowledge the Graphic Era (Deemed to be) University for sustainable research support.

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Authors and Affiliations

  1. School of Pharmacy, Graphic Era Hill University, Dehradun, 248002, India

    Indu Singh

  2. Department of Biotechnology, Graphic Era (Deemed to be) University, Dehradun, 248002, India

    Indu Singh & Divakar Sharma

  3. School of Life Science, Jaipur National University, Jaipur, India

    Juhi Sharma

  4. Department of Zoology, Sanatan Dharm College, Muzaffarnagar, 251001, India

    Arun Ratn

  5. Department of Biochemistry, ICMR-National JALMA Institute for Leprosy and other Mycobacterial Diseases, Tajganj, Agra, India

    Deepa Bisht

  6. Department of Medical Laboratory Sciences, Lovely Professional University, Phagwara, India

    Sandeep Sharma

  7. Department of Microbiology, Maulana Azad Medical College and Associated Hospital, New Delhi, 110002, India

    Megh Singh Dhakad

  8. Department of Pharmacology, Faculty of Medicine and Health Sciences, SGT University, Gurugram, Haryana, India

    Jasbir Dalal

  9. Faculty of Medicine, Alatoo International University, Bishkek, Kyrgyzstan

    Mirza Masroor Ali Beg

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  3. Divakar Sharma
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  7. Megh Singh Dhakad
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  8. Jasbir Dalal
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  9. Mirza Masroor Ali Beg
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Contributions

DS conceived the idea. DS, IS, and JS curated data, wrote the initial draft, and prepared the figures. DS, MSD, AR, JD, MMAB, SS, and DB reviewed the manuscript. All authors approved the final version of the manuscript.

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Correspondence to Divakar Sharma.

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Singh, I., Sharma, J., Sharma, D. et al. Bedaquiline Resistance: A Looming Global Threat in Tuberculosis Management. Curr Microbiol 83, 57 (2026). https://doi.org/10.1007/s00284-025-04655-7

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