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Microbiology Society logo Microbiology

Volume 170, Issue 8

Identification of gene targets that potentiate the action of rifampicin on BCG Open Access

Abstract

Tuberculosis (TB) caused by bacteria of the complex remains one of the most important infectious diseases of mankind. Rifampicin is a first line drug used in multi-drug treatment of TB, however, the necessary duration of treatment with these drugs is long and development of resistance is an increasing impediment to treatment programmes. As a result, there is a requirement for research and development of new TB drugs, which can form the basis of new drug combinations, either due to their own anti-mycobacterial activity or by augmenting the activity of existing drugs such as rifampicin. This study describes a TnSeq analysis to identify mutants with enhanced sensitivity to sub-minimum inhibitory concentrations (MIC) of rifampicin. The rifampicin-sensitive mutants were disrupted in genes of a variety of functions and the majority fitted into three thematic groups: firstly, genes that were involved in DNA/RNA metabolism, secondly, genes involved in sensing and regulating mycobacterial cellular systems, and thirdly, genes involved in the synthesis and maintenance of the cell wall. Selection at two concentrations of rifampicin (1/250 and 1/62 MIC) demonstrated a dose response for mutants with statistically significant sensitivity to rifampicin. The dataset reveals mechanisms of how mycobacteria are innately tolerant to and initiate an adaptive response to rifampicin; providing putative targets for the development of adjunctive therapies that potentiate the action of rifampicin.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Mycobacterium tuberculosis , ParB , PknE , rifampicin , Rnase HI , TnSeq and transposon sequencing
Funding
This study was supported by the:
  • Biotechnology and Biological Sciences Research Council (Award BB/W016613/1)
    • Principal Award Recipient: GrahamR. Stewart
  • Commonwealth Scholarship Commission (Award FJCS-2018-138)
    • Principal Award Recipient: PoojaChand
© 2024 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2024-08-16
2025-12-13

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/content/journal/micro/10.1099/mic.0.001488
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Identification of gene targets that potentiate the action of rifampicin on Mycobacterium bovis BCG
Microbiology 170, 001488 (2024); https://doi.org/10.1099/mic.0.001488
/content/journal/micro/10.1099/mic.0.001488
/content/journal/micro/10.1099/mic.0.001488
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