- Mycobacterial Regulatory Systems Involved in the Regulation of Gene Expression Under Respiration‑Inhibitory Conditions
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Yuna Oh , Ha-Na Lee , Eon-Min Ko , Ji-A Jeong , Sae Woong Park , Jeong-Il Oh
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J. Microbiol. 2023;61(3):297-315. Published online February 27, 2023
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DOI: https://doi.org/10.1007/s12275-023-00026-8
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Mycobacterium tuberculosis is the causative agent of tuberculosis. M. tuberculosis can survive in a dormant state within
the granuloma, avoiding the host-mounting immune attack. M. tuberculosis bacilli in this state show increased tolerance
to antibiotics and stress conditions, and thus the transition of M. tuberculosis to the nonreplicating dormant state acts as
an obstacle to tuberculosis treatment. M. tuberculosis in the granuloma encounters hostile environments such as hypoxia,
nitric oxide, reactive oxygen species, low pH, and nutrient deprivation, etc., which are expected to inhibit respiration of M.
tuberculosis. To adapt to and survive in respiration-inhibitory conditions, it is required for M. tuberculosis to reprogram its
metabolism and physiology. In order to get clues to the mechanism underlying the entry of M. tuberculosis to the dormant
state, it is important to understand the mycobacterial regulatory systems that are involved in the regulation of gene expression
in response to respiration inhibition. In this review, we briefly summarize the information regarding the regulatory
systems implicated in upregulation of gene expression in mycobacteria exposed to respiration-inhibitory conditions. The
regulatory systems covered in this review encompass the DosSR (DevSR) two-component system, SigF partner switching
system, MprBA-SigE-SigB signaling pathway, cAMP receptor protein, and stringent response.
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Citations
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Feng Chen, Yifan Shen, Qianhui Yan, Daishan Zheng, Xiaoli Chen, Longyu Fang, Mengchen Sun, Yuansi Zhang, Maoping Chu, Enhui Yang, Xiu-Feng Huang
Annals of Medicine.2026;[Epub] CrossRef - Recent advances in research on Mycobacterium tuberculosis virulence factors and their role in pathogenesis
Ming-Rui Sun, Jia-Yin Xing, Xiao-Tian Li, Ren Fang, Yang Zhang, Zhao-Li Li, Ning-Ning Song
Journal of Microbiology, Immunology and Infection.2025; 58(5): 497. CrossRef - Host Immune Pathways to Mycobacterium tuberculosis Infection
Eun-Jin Park, Insoo Kim, Eun-Kyeong Jo
Journal of Bacteriology and Virology.2024; 54(3): 167. CrossRef - Bacterial Regulatory Mechanisms for the Control of Cellular Processes: Simple Organisms’ Complex Regulation
Jin-Won Lee
Journal of Microbiology.2023; 61(3): 273. CrossRef
- Negative regulation of the acsA1 gene encoding the major acetyl-CoA synthetase by cAMP receptor protein in Mycobacterium smegmatis
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Eon-Min Ko , Yuna Oh , Jeong-Il Oh
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J. Microbiol. 2022;60(12):1139-1152. Published online October 24, 2022
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DOI: https://doi.org/10.1007/s12275-022-2347-x
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Acetyl-CoA synthetase (ACS) is the enzyme that irreversibly
catalyzes the synthesis of acetyl-CoA from acetate, CoA-SH,
and ATP via acetyl-AMP as an intermediate. In this study,
we demonstrated that AcsA1 (MSMEG_6179) is the predominantly
expressed ACS among four ACSs (MSMEG_6179,
MSMEG_0718, MSMEG_3986, and MSMEG_5650) found
in Mycobacterium smegmatis and that a deletion mutation
of acsA1 in M. smegmatis led to its compromised growth on
acetate as the sole carbon source. Expression of acsA1 was
demonstrated to be induced during growth on acetate as the
sole carbon source. The acsA1 gene was shown to be negatively
regulated by Crp1 (MSMEG_6189) that is the major
cAMP receptor protein (CRP) in M. smegmatis. Using DNase
I footprinting analysis and site-directed mutagenesis, a CRPbinding
site (GGTGA-N6-TCACA) was identified in the upstream
regulatory region of acsA1, which is important for repression
of acsA1 expression. We also demonstrated that inhibition
of the respiratory electron transport chain by inactivation
of the major terminal oxidase, aa3 cytochrome c oxidase,
led to a decrease in acsA1 expression probably through
the activation of CRP. In conclusion, AcsA1 is the major ACS
in M. smegmatis and its gene is under the negative regulation
of Crp1, which contributes to some extent to the induction
of acsA1 expression under acetate conditions. The growth of
M. smegmatis is severely impaired on acetate as the sole carbon
source under respiration-inhibitory conditions.
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Yanan Zhou, Xue-Xian Zhang, Dandan Wang, Mengguang Zhao, Li Sun, Weiwei Huang, Zhihong Xie
Microbiological Research.2026; 304: 128413. CrossRef - Inhibitory activity and antioomycete mechanism of citral against Phytophthora capsici
Kaidi Cui, Yinan Wang, Mengke Wang, Te Zhao, Fulong Zhang, Leiming He, Lin Zhou
Pesticide Biochemistry and Physiology.2024; 204: 106067. 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
- 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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Yuna Oh , Hye-In Lee , Ji-A Jeong , Seonghan Kim , Jeong-Il Oh
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J. Microbiol. 2022;60(9):935-947. Published online August 1, 2022
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DOI: https://doi.org/10.1007/s12275-022-2202-0
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868
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Abstract
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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.
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Chemical Engineering Journal.2026; 529: 172994. CrossRef - Regulatory mechanism of the SenX3-RegX3 two-component system in Mycobacterium smegmatis: Roles of PhoU in sensing inorganic phosphate levels
Youjin Seung, Ha-Eun Baik, Eun-Jin Park, Jeong-Il Oh
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
Barbora Brezovská, Subhash Narasimhan, Michaela Šiková, Hana Šanderová, Tomáš Kovaľ, Nabajyoti Borah, Mahmoud Shoman, Debora Pospíšilová, Viola Vaňková Hausnerová, Dávid Tužinčin, Martin Černý, Jan Komárek, Martina Janoušková, Milada Kambová, Petr Halada,
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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