| Title | Activation of the SigE-SigB signaling pathway by inhibition of the respiratory electron transport chain and its effect on rifampicin resistance in Mycobacterium smegmatis |
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| Author | Yuna Oh1, Hye-In Lee1, Ji-A Jeong2, Seonghan Kim2, and Jeong-Il Oh1,3* |
| Address | 1Department of Integrated Biological Science, Pusan National University, Busan 46241, Republic of Korea, 2Division of Bacterial Disease Research, Center for Infectious Disease Research, National Institute of Infectious Diseases, National Institute of Health, Korea Disease Control and Prevention Agency, Osong 28159, Republic of Korea, 3Microbiological Resource Research Institute, Pusan National University, Busan 46241, Republic of Korea |
| Bibliography | Journal of Microbiology, 60(9),935-947, 2022, |
| DOI | 10.1007/s12275-022-2202-0 |
| Key Words | aa3 cytochrome c oxidase, antibiotics, electron transport chain, Mycobacterium, regulation of gene expression, rifampicin, SigB, SigE, sigma factor |
| Abstract | 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. |