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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

  • Microbial Genetics, Genomics and Molecular Biology
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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 pho U2 (MSMEG_1605) gene implicated in a phosphate-signaling 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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References

  • Abdelwahab, H., Martin Del Campo, J.S., Dai, Y., Adly, C., El-Sohaimy, S., and Sobrado, P. 2016. Mechanism of Rifampicin Inactivation in Nocardia farcinica. PLoS ONE 11, e0162578.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Alexander, D.C., Jones, J.R., and Liu, J. 2003. A rifampin-hypersensitive mutant reveals differences between strains of Mycobacterium smegmatis and presence of a novel transposon, IS1623. Antimicrob. Agents Chemother. 47, 3208–3213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baek, S.H., Li, A.H., and Sassetti, C.M. 2011. Metabolic regulation of mycobacterial growth and antibiotic sensitivity. PLoS Biol. 9, e1001065.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baker, J.J. and Abramovitch, R.B. 2018. Genetic and metabolic regulation of Mycobacterium tuberculosis acid growth arrest. Sci. Rep. 8, 4168.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barik, S., Sureka, K., Mukherjee, P., Basu, J., and Kundu, M. 2010. RseA, the SigE specific anti-sigma factor of Mycobacterium tuberculosis, is inactivated by phosphorylation-dependent ClpC1P2 proteolysis. Mol. Microbiol. 75, 592–606.

    Article  CAS  PubMed  Google Scholar 

  • Baysarowich, J., Koteva, K., Hughes, D.W., Ejim, L., Griffiths, E., Zhang, K., Junop, M., and Wright, G.D. 2008. Rifamycin antibiotic resistance by ADP-ribosylation: structure and diversity of Arr. Proc. Natl. Acad. Sci. USA 105, 4886–4891.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Belanger, A.E., Besra, G.S., Ford, M.E., Mikusová, K., Belisle, J.T., Brennan, P.J., and Inamine, J.M. 1996. The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol. Proc. Natl. Acad. Sci. USA 93, 11919–11924.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Belevich, I., Borisov, V.B., Bloch, D.A., Konstantinov, A.A., and Verkhovsky, M.I. 2007. Cytochrome bd from Azotobacter vinelandii: evidence for high-affinity oxygen binding. Biochemistry 46, 11177–11184.

    Article  CAS  PubMed  Google Scholar 

  • Betts, J.C., Lukey, P.T., Robb, L.C., McAdam, R.A., and Duncan, K. 2002. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol. Microbiol. 43, 717–731.

    Article  CAS  PubMed  Google Scholar 

  • Boldrin, F., Cioetto Mazzabò, L., Anoosheh, S., Palù, G., Gaudreau, L., Manganelli, R., and Provvedi, R. 2019. Assessing the role of Rv1222 (RseA) as an anti-sigma factor of the Mycobacterium tuberculosis extracytoplasmic sigma factor SigE. Sci. Rep. 9, 4513.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brokaw, A.M., Eide, B.J., Muradian, M., Boster, J.M., and Tischler, A.D. 2017. Mycobacterium smegmatis PhoU proteins have overlapping functions in phosphate signaling and are essential. Front. Microbiol. 8, 2523.

    Article  PubMed  PubMed Central  Google Scholar 

  • Campbell, E.A., Korzheva, N., Mustaev, A., Murakami, K., Nair, S., Goldfarb, A., and Darst, S.A. 2001. Structural mechanism for rifampicin inhibition of bacterial RNA polymerase. Cell 104, 901–912.

    Article  CAS  PubMed  Google Scholar 

  • Casonato, S., Provvedi, R., Dainese, E., Palù, G., and Manganelli, R. 2014. Mycobacterium tuberculosis requires the ECF sigma factor SigE to arrest phagosome maturation. PLoS ONE 9, e108893.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chauhan, R., Ravi, J., Datta, P., Chen, T., Schnappinger, D., Bassler, K.E., Balázsi, G., and Gennaro, M.L. 2016. Reconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis. Nat. Commun. 7, 11062.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, P., Ruiz, R.E., Li, Q., Silver, R.F., and Bishai, W.R. 2000. Construction and characterization of a Mycobacterium tuberculosis mutant lacking the alternate sigma factor gene, sigF. Infect. Immun. 68, 5575–5580.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chopra, I. and Roberts, M. 2001. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol. Mol. Biol. Rev. 65, 232–260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cole, S.T., Brosch, R., Parkhill, J., Garnier, T., Churcher, C., Harris, D., Gordon, S.V., Eiglmeier, K., Gas, S., Barry, C.E.3rd, et al. 1998. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544.

    Article  CAS  PubMed  Google Scholar 

  • Dainese, E., Rodrigue, S., Delogu, G., Provvedi, R., Laflamme, L., Brzezinski, R., Fadda, G., Smith, I., Gaudreau, L., Palu, G., et al. 2006. Posttranslational regulation of Mycobacterium tuberculosis extracytoplasmic-function sigma factor sL and roles in virulence and in global regulation of gene expression. Infect. Immun. 74, 2457–2461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davis, B.D. 1987. Mechanism of bactericidal action of aminoglycosides. Microbiol. Rev. 51, 341–350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Drlica, K. and Zhao, X. 1997. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol. Mol. Biol. Rev. 61, 377–392.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dussurget, O., Rodriguez, M., and Smith, I. 1998. Protective role of the Mycobacterium smegmatis IdeR against reactive oxygen species and isoniazid toxicity. Tuber. Lung Dis. 79, 99–106.

    Article  CAS  PubMed  Google Scholar 

  • Dutta, N.K. and Karakousis, P.C. 2014. Latent tuberculosis infection: myths, models, and molecular mechanisms. Microbiol. Mol. Biol. Rev. 78, 343–371.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ehlers, S. and Schaible, U.E. 2012. The granuloma in tuberculosis: dynamics of a host-pathogen collusion. Front. Immunol. 3, 411.

    PubMed  Google Scholar 

  • Fontan, P.A., Voskuil, M.I., Gomez, M., Tan, D., Pardini, M., Manganelli, R., Fattorini, L., Schoolnik, G.K., and Smith, I. 2009. The Mycobacterium tuberculosis sigma factor sB is required for full response to cell envelope stress and hypoxia in vitro, but it is dispensable for in vivo growth. J. Bacteriol. 191, 5628–5633.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gengenbacher, M., Rao, S.P.S., Pethe, K., and Dick, T. 2010. Nutrient-starved, non-replicating Mycobacterium tuberculosis requires respiration, ATP synthase and isocitrate lyase for maintenance of ATP homeostasis and viability. Microbiology 156, 81–87.

    Article  CAS  PubMed  Google Scholar 

  • Goldstein, B.P. 2014. Resistance to rifampicin: a review. J. Antibiot. 67, 625–630.

    Article  CAS  Google Scholar 

  • Grant, S.S., Kaufmann, B.B., Chand, N.S., Haseley, N., and Hung, D.T. 2012. Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals. Proc. Natl. Acad. Sci. USA 109, 12147–12152.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Green, M.R. and Sambrook, J. 2012. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, USA.

    Google Scholar 

  • Gruber, T.M. and Gross, C.A. 2003. Multiple sigma subunits and the partitioning of bacterial transcription space. Annu Rev. Microbiol. 57, 441–466.

    Article  CAS  PubMed  Google Scholar 

  • Harding, E. 2020. WHO global progress report on tuberculosis elimination. Lancet Respir. Med. 8, 19.

    Article  PubMed  Google Scholar 

  • Hernandez Pando, R., Aguilar, L.D., Smith, I., and Manganelli, R. 2010. Immunogenicity and protection induced by a Mycobacterium tuberculosis sigE mutant in a BALB/c mouse model of progressive pulmonary tuberculosis. Infect. Immun. 78, 3168–3176.

    Article  PubMed  CAS  Google Scholar 

  • Hooper, D.C., Wolfson, J.S., Ng, E.Y., and Swartz, M.N. 1987. Mechanisms of action of and resistance to ciprofloxacin. Am. J. Med. 82, 12–20.

    CAS  PubMed  Google Scholar 

  • Hu, Y., Morichaud, Z., Perumal, A.S., Roquet-Baneres, F., and Brodolin, K. 2014. Mycobacterium RbpA cooperates with the stress-response sB subunit of RNA polymerase in promoter DNA unwinding. Nucleic Acids Res. 42, 10399–10408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hurst-Hess, K., Biswas, R., Yang, Y., Rudra, P., Lasek-Nesselquist, E., and Ghosh, P. 2019. Mycobacterial SigA and SigB cotranscribe essential housekeeping genes during exponential growth. mBio 10, e00273–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeong, J.A., Park, S.W., Yoon, D., Kim, S., Kang, H.Y., and Oh, J.I. 2018. Roles of alanine dehydrogenase and induction of its gene in Mycobacterium smegmatis under respiration-inhibitory conditions. J. Bacteriol. 200, e00152–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kana, B.D., Weinstein, E.A., Avarbock, D., Dawes, S.S., Rubin, H., and Mizrahi, V. 2001. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 183, 7076–7086.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keren, I., Minami, S., Rubin, E., and Lewis, K. 2011. Characterization and transcriptome analysis of Mycobacterium tuberculosis persisters. mBio 2, e00100–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kim, M.J., Park, K.J., Ko, I.J., Kim, Y.M., and Oh, J.I. 2010. Different roles of DosS and DosT in the hypoxic adaptation of Mycobacteria. J. Bacteriol. 192, 4868–4875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ko, E.M. and Oh, J.I. 2020. Induction of the cydAB operon encoding the bd quinol oxidase under respiration-inhibitory conditions by the major cAMP receptor protein MSMEG_6189 in Mycobacterium smegmatis. Front. Microbiol. 11, 608624.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kohanski, M.A., Dwyer, D.J., Hayete, B., Lawrence, C.A., and Collins, J.J. 2007. A common mechanism of cellular death induced by bactericidal antibiotics. Cell 130, 797–810.

    Article  CAS  PubMed  Google Scholar 

  • Lee, B.S., Kalia, N.P., Jin, X.E.F., Hasenoehrl, E.J., Berney, M., and Pethe, K. 2019. Inhibitors of energy metabolism interfere with antibiotic-induced death in mycobacteria. J. Biol. Chem. 294, 1936–1943.

    Article  CAS  PubMed  Google Scholar 

  • Lee, J.H., Karakousis, P.C., and Bishai, W.R. 2008. Roles of SigB and SigF in the Mycobacterium tuberculosis sigma factor network. J. Bacteriol. 190, 699–707.

    Article  CAS  PubMed  Google Scholar 

  • Manganelli, R., Fattorini, L., Tan, D., Iona, E., Orefici, G., Altavilla, G., Cusatelli, P., and Smith, I. 2004a. The extra cytoplasmic function sigma factor sE is essential for Mycobacterium tuberculosis virulence in mice. Infect. Immun. 72, 3038–3041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manganelli, R., Provvedi, R., Rodrigue, S., Beaucher, J., Gaudreau, L., and Smith, I. 2004b. A Factors and global gene regulation in Mycobacterium tuberculosis. J. Bacteriol. 186, 895–902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manganelli, R., Voskuil, M.I., Schoolnik, G.K., Dubnau, E., Gomez, M., and Smith, I. 2002. Role of the extracytoplasmic-function s factor sH in Mycobacterium tuberculosis global gene expression. Mol. Microbiol. 45, 365–374.

    Article  CAS  PubMed  Google Scholar 

  • Manganelli, R., Voskuil, M.I., Schoolnik, G.K., and Smith, I. 2001. The Mycobacterium tuberculosis ECF sigma factor σE: role in global gene expression and survival in macrophages. Mol. Microbiol. 41, 423–437.

    Article  CAS  PubMed  Google Scholar 

  • Martini, M.C., Zhou, Y., Sun, H., and Shell, S.S. 2019. Defining the transcriptional and post-transcriptional landscapes of Mycobacterium smegmatis in aerobic growth and hypoxia. Front. Microbiol. 10, 591.

    Article  PubMed  PubMed Central  Google Scholar 

  • Matsoso, L.G., Kana, B.D., Crellin, P.K., Lea-Smith, D.J., Pelosi, A., Powell, D., Dawes, S.S., Rubin, H., Coppel, R.L., and Mizrahi, V. 2005. Function of the cytochrome bc1-aa3 branch of the respiratory network in Mycobacteria and network adaptation occurring in response to its disruption. J. Bacteriol. 187, 6300–6308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Megehee, J.A., Hosler, J.P., and Lundrigan, M.D. 2006. Evidence for a cytochrome bcc-aa3interaction in the respiratory chain of Mycobacterium smegmatis. Microbiology 152, 823–829.

    Article  CAS  PubMed  Google Scholar 

  • Mouncey, N.J. and Kaplan, S. 1998. Redox-dependent gene regulation in Rhodobacter sphaeroides 2.4.1T: effects on dimethyl sulfoxide reductase (dor) gene expression. J. Bacteriol. 180, 5612–5618.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mukherjee, R. and Chatterji, D. 2005. Evaluation of the role of sigma B in Mycobacterium smegmatis. Biochem. Biophys. Res. Commun. 338, 964–972.

    Article  CAS  PubMed  Google Scholar 

  • Namugenyi, S.B., Aagesen, A.M., Elliott, S.R., and Tischler, A.D. 2017. Mycobacterium tuberculosis PhoY proteins promote persister formation by mediating Pst/SenX3-RegX3 phosphate sensing. mBio 8, e00494–17.

    Article  PubMed  PubMed Central  Google Scholar 

  • Nathan, C. and Barry, C.E. 2015. TB drug development: immunology at the table. Immunol. Rev. 264, 308–318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oh, J.I. and Kaplan, S. 1999. The cbb3 terminal oxidase of Rhodobacter sphaeroides 2.4.1: structural and functional implications for the regulation of spectral complex formation. Biochemistry 38, 2688–2696.

    Article  CAS  PubMed  Google Scholar 

  • Oh, Y., Song, S.Y., Kim, H.J., Han, G., Hwang, J., Kang, H.Y., and Oh, J.I. 2020. The partner switching system of the SigF sigma factor in Mycobacterium smegmatis and induction of the SigF regulon under respiration-inhibitory conditions. Front. Microbiol. 11, 588487.

    Article  PubMed  PubMed Central  Google Scholar 

  • Paget, M.S. 2015. Bacterial sigma factors and anti-sigma factors: structure, function and distribution. Biomolecules 5, 1245–1265.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paget, M.S.B. and Helmann, J.D. 2003. The s70 family of sigma factors. Genome Biol. 4, 203.

    Article  PubMed  PubMed Central  Google Scholar 

  • Piccaro, G., Giannoni, F., Filippini, P., Mustazzolu, A., and Fattorini, L. 2013. Activities of drug combinations against Mycobacterium tuberculosis grown in aerobic and hypoxic acidic conditions. Antimicrob. Agents Chemother. 57, 1428–1433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pisu, D., Provvedi, R., Espinosa, D.M., Payan, J.B., Boldrin, F., Palù, G., Hernandez-Pando, R., and Manganelli, R. 2017. The alternative sigma factors SigE and SigB are involved in tolerance and persistence to antitubercular drugs. Antimicrob. Agents Chemother. 61, e01596–17.

    Article  PubMed  PubMed Central  Google Scholar 

  • Poehlsgaard, J. and Douthwaite, S. 2005. The bacterial ribosome as a target for antibiotics. Nat. Rev. Microbiol. 3, 870–881.

    Article  CAS  PubMed  Google Scholar 

  • Puustinen, A., Finel, M., Haltia, T., Gennis, R.B., and Wikstrom, M. 1991. Properties of the two terminal oxidases of Escherichia coli. Biochemistry 30, 3936–3942.

    Article  CAS  PubMed  Google Scholar 

  • Raman, S., Song, T., Puyang, X., Bardarov, S., Jacobs, W.R.Jr, and Husson, R.N. 2001. The alternative sigma factor SigH regulates major components of oxidative and heat stress responses in Mycobacterium tuberculosis. J. Bacteriol. 183, 6119–6125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rawat, R., Whitty, A., and Tonge, P.J. 2003. The isoniazid-NAD adduct is a slow, tight-binding inhibitor of InhA, the Mycobacterium tuberculosis enoyl reductase: adduct affinity and drug resistance. Proc. Natl. Acad. Sci. USA 100, 13881–13886.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodrigue, S., Provvedi, R., Jacques, P.E., Gaudreau, L., and Manganelli, R. 2006. The a factors of Mycobacterium tuberculosis. FEMS Microbiol. Rev. 30, 926–941.

    Article  CAS  PubMed  Google Scholar 

  • Sachdeva, P., Misra, R., Tyagi, A.K., and Singh, Y. 2010. The sigma factors of Mycobacterium tuberculosis: regulation of the regulators. FEBS J. 277, 605–626.

    Article  CAS  PubMed  Google Scholar 

  • Safi, H., Sayers, B., Hazbón, M.H., and Alland, D. 2008. Transfer of embB codon 306 mutations into clinical Mycobacterium tuberculosis strains alters susceptibility to ethambutol, isoniazid, and rifampin. Antimicrob. Agents Chemother. 52, 2027–2034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi, W. and Zhang, Y. 2010. PhoY2 but not PhoY1 is the PhoU homologue involved in persisters in Mycobacterium tuberculosis. J. Antimicrob. Chemother. 65, 1237–1242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Snapper, S.B., Melton, R.E., Mustafa, S., Kieser, T., and Jacobs, W.R.Jr. 1990. Isolation and characterization of efficient plasmid transformation mutants of Mycobacterium smegmatis. Mol. Microbiol. 4, 1911–1919.

    Article  CAS  PubMed  Google Scholar 

  • Song, T., Song, S.E., Raman, S., Anaya, M., and Husson, R.N. 2008. Critical role of a single position in the -35 element for promoter recognition by Mycobacterium tuberculosis SigE and SigH. J. Bacteriol. 190, 2227–2230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spanogiannopoulos, P., Thaker, M., Koteva, K., Waglechner, N., and Wright, G.D. 2012. Characterization of a rifampin-inactivating glycosyltransferase from a screen of environmental actinomycetes. Antimicrob. Agents Chemother. 56, 5061–5069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sureka, K., Dey, S., Datta, P., Singh, A.K., Dasgupta, A., Rodrigue, S., Basu, J., and Kundu, M. 2007. Polyphosphate kinase is involved in stress-induced mprAB-sigE-rel signalling in mycobacteria. Mol. Microbiol. 65, 261–276.

    Article  CAS  PubMed  Google Scholar 

  • Surette, M.D., Spanogiannopoulos, P., and Wright, G.D. 2021. The enzymes of the rifamycin antibiotic resistome. Acc. Chem. Res. 54, 2065–2075.

    Article  CAS  PubMed  Google Scholar 

  • Via, L.E., Lin, P.L., Ray, S.M., Carrillo, J., Allen, S.S., Eum, S.Y., Taylor, K., Klein, E., Manjunatha, U., Gonzales, J., et al. 2008. Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates. Infect. Immun. 76, 2333–2340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vilchèze, C., Hartman, T., Weinrick, B., Jain, P., Weisbrod, T.R., Leung, L.W., Freundlich, J.S., and Jacobs, W.R.Jr. 2017. Enhanced respiration prevents drug tolerance and drug resistance in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 114, 4495–4500.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vilchèze, C., Morbidoni, H.R., Weisbrod, T.R., Iwamoto, H., Kuo, M., Sacchettini, J.C., and Jacobs, W.R.Jr. 2000. Inactivation of the inhA-encoded fatty acid synthase II (FASII) enoyl-acyl carrier protein reductase induces accumulation of the FASI end products and cell lysis of Mycobacterium smegmatis. J. Bacteriol. 182, 4059–4067.

    Article  PubMed  PubMed Central  Google Scholar 

  • Viswanathan, G., Yadav, S., and Raghunand, T.R. 2016. Identification of novel loci associated with mycobacterial isoniazid resistance. Tuberculosis 96, 21–26.

    Article  CAS  PubMed  Google Scholar 

  • Waagmeester, A., Thompson, J., and Reyrat, J.M. 2005. Identifying sigma factors in Mycobacterium smegmatis by comparative genomic analysis. Trends Microbiol. 13, 505–509.

    Article  CAS  PubMed  Google Scholar 

  • Wang, L., Feng, Z., Wang, X., Wang, X., and Zhang, X. 2010. DEGseq: an R package for identifying differentially expressed genes from RNA-seq data. Bioinformatics 26, 136–138.

    Article  PubMed  CAS  Google Scholar 

  • Wayne, L.G. and Hayes, L.G. 1996. An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect. Immun. 64, 2062–2069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wayne, L.G. and Sohaskey, C.D. 2001. Nonreplicating persistence of Mycobacterium tuberculosis. Annu Rev. Microbiol. 55, 139–163.

    Article  CAS  PubMed  Google Scholar 

  • Wilson, T.M. and Collins, D.M. 1996. ahpC, a gene involved in isoniazid resistance of the Mycobacterium tuberculosis complex. Mol. Microbiol. 19, 1025–1034.

    Article  CAS  PubMed  Google Scholar 

  • Wu, Q.L., Kong, D., Lam, K., and Husson, R.N. 1997. A mycobacterial extracytoplasmic function sigma factor involved in survival following stress. J. Bacteriol. 179, 2922–2929.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang, S.S., Hu, Y.B., Wang, X.D., Gao, Y.R., Li, K., Zhang, X.E., Chen, S.Y., Zhang, T.Y., Gu, J., and Deng, J.Y. 2017. Deletion of sigB causes increased sensitivity to para-aminosalicylic acid and sulfamethoxazole in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 61, e00551–17.

    CAS  Google Scholar 

  • Yazawa, K., Mikami, Y., Maeda, A., Akao, M., Morisaki, N., and Iwasaki, S. 1993. Inactivation of rifampin by Nocardia brasiliensis. Antimicrob. Agents Chemother. 37, 1313–1317.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeng, S., Soetaert, K., Ravon, F., Vandeput, M., Bald, D., Kauffmann, J.M., Mathys, V., Wattiez, R., and Fontaine, V. 2019. Isoniazid bactericidal activity involves electron transport chain perturbation. Antimicrob. Agents Chemother. 63, e01841–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zumla, A., Nahid, P., and Cole, S.T. 2013. Advances in the development of new tuberculosis drugs and treatment regimens. Nat. Rev. Drug Discov. 12, 388–404.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded mainly by the Ministry of Education, Science and Technology (NRF-2020R1A2C1005305) to JI Oh and in part by the National Institute of Health research project (2020-NG-005-01) to S Kim.

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  1. Department of Integrated Biological Science, Pusan National University, Busan, 46241, Korea

    Yuna Oh, Hye-In Lee & Jeong-Il Oh

  2. Division 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, Korea

    Ji-A Jeong & Seonghan Kim

  3. Microbiological Resource Research Institute, Pusan National University, Busan, 46241, Korea

    Jeong-Il Oh

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  1. Yuna Oh
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Oh, Y., Lee, HI., Jeong, JA. et al. Activation of the SigE-SigB signaling pathway by inhibition of the respiratory electron transport chain and its effect on rifampicin resistance in Mycobacterium smegmatis. J Microbiol. 60, 935–947 (2022). https://doi.org/10.1007/s12275-022-2202-0

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