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Activation of the SigE-SigB signaling pathway by inhibition of the respiratory electron transport chain and its effect on rifampicin resistance in Mycobacterium smegmatis
Yuna Oh , Hye-In Lee , Ji-A Jeong , Seonghan Kim , Jeong-Il Oh
J. Microbiol. 2022;60(9):935-947.   Published online August 1, 2022
DOI: https://doi.org/10.1007/s12275-022-2202-0
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AbstractAbstract PDF
Using a mutant of Mycobacterium smegmatis lacking the major aa3 cytochrome c oxidase of the electron transport chain (Δaa3), we demonstrated that inhibition of the respiratory electron transport chain led to an increase in antibiotic resistance of M. smegmatis to isoniazid, rifampicin, ethambutol, and tetracycline. The alternative sigma factors SigB and SigE were shown to be involved in an increase in rifampicin resistance of M. smegmatis induced under respiration-inhibitory conditions. As in Mycobacterium tuberculosis, SigE and SigB form a hierarchical regulatory pathway in M. smegmatis through SigE-dependent transcription of sigB. Expression of sigB and sigE was demonstrated to increase in the Δaa3 mutant, leading to upregulation of the SigB-dependent genes in the mutant. The phoU2 (MSMEG_1605) gene implicated in a phosphatesignaling pathway and the MSMEG_1097 gene encoding a putative glycosyltransferase were identified to be involved in the SigB-dependent enhancement of rifampicin resistance observed for the Δaa3 mutant of M. smegmatis. The significance of this study is that the direct link between the functionality of the respiratory electron transport chain and antibiotic resistance in mycobacteria was demonstrated for the first time using an electron transport chain mutant rather than inhibitors of electron transport chain.

Citations

Citations to this article as recorded by  
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    Chemical Engineering Journal.2026; 529: 172994.     CrossRef
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    Journal of Biological Chemistry.2025; 301(8): 110435.     CrossRef
  • Inactivation of cAMP receptor protein (MSMEG_6189) increases isoniazid susceptibility in Mycobacterium smegmatis via altered oxidative phosphorylation, elevated ROS production, and loss of ahpC
    Narin Kim, Yuna Oh, Jeong-Il Oh, Tina M. Henkin
    Journal of Bacteriology.2025;[Epub]     CrossRef
  • Rel-dependent decrease in the expression of ribosomal protein genes by inhibition of the respiratory electron transport chain in Mycobacterium smegmatis
    Na-Kyeong Kim, Jong-Eun Baek, Ye-Jin Lee, Yuna Oh, Jeong-Il Oh
    Frontiers in Microbiology.2024;[Epub]     CrossRef
  • MoaB2, a newly identified transcription factor, binds to σ A in Mycobacterium smegmatis
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    Journal of Bacteriology.2024;[Epub]     CrossRef
  • Enhanced hypoxanthine utilization for cAMP salvage synthesis efficiently by Arthrobacter sp. CCTCC 2013431 via xanthine oxidase inhibition
    Baofeng Chen, Hai Tan, Chang Li, Linbo Li, Zhonghua Zhang, Zhigang Li
    Biotechnology Letters.2024; 46(6): 1095.     CrossRef
  • Mycobacterial Regulatory Systems Involved in the Regulation of Gene Expression Under Respiration-Inhibitory Conditions
    Yuna Oh, Ha-Na Lee, Eon-Min Ko, Ji-A Jeong, Sae Woong Park, Jeong-Il Oh
    Journal of Microbiology.2023; 61(3): 297.     CrossRef

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