FadR subfamily of transcriptional regulators are dispensable for the pathogenesis of Mycobacterium tuberculosis

Saurabh Chugh

doi:10.1016/j.tube.2026.102796

FadR subfamily of transcriptional regulators are dispensable for the pathogenesis of Mycobacterium tuberculosis

2026-07-11

0

PRE

AI

S

Saurabh Chugh

B

Bhupinder Singh

N

Neeraj Kumar Chauhan

D

Deepika Chaudhary

M

Manisha Singh

A

Arun Sharma

M

Munmun Bhasin

N

null Niharika

P

Pankaj Chopra

M

Manisha Priya

V

Vijay Singh

R

Raghavan Varadarajan

R

Ramandeep Singh

DOI：10.1016/j.tube.2026.102796

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Abstract

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A diverse set of transcriptional regulators (TRs) enables Mycobacterium tuberculosis (M. tuberculosis) to reprogram its gene expression profiles to adapt and counteract the challenges imposed by the host during infection. FadR subfamily TRs regulate different physiological aspects of bacteria, including stress adaptation and virulence. The genome of M. tuberculosis encodes five homologs of the FadR subfamily of TRs. Here, we have comprehensively characterised the three FadR subfamily TRs, namely Rv0043c, Rv0165c, and Rv3060c, to assess their role in M. tuberculosis stress adaptation and pathogenesis. We demonstrate that the individual deletion of these TRs does not affect the growth of M. tuberculosis in vitro under various host-mimicking stress conditions or during infection of macrophages, mice, or guinea pigs. RNA-seq analysis revealed that, compared to the wild type strain, the relative transcript levels of the majority of differentially expressed genes were increased in the ΔRv0043c, ΔRv0165c and ΔRv3060c strains of M. tuberculosis, suggesting that these proteins function as transcriptional repressors. Taken together, these results suggest that functional redundancy exists between the FadR subfamily of TRs.

FadR subfamily of transcriptional regulators are dispensable for the pathogenesis of Mycobacterium tuberculosis

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