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2019, Number 3

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VacciMonitor 2019; 28 (3)

Regulators of Mycobacterium tuberculosis gene expression: implications in virulence and persistence in latent tuberculosis

Méndez-López MV

Language: Spanish
References: 57
Page: 110-120
PDF size: 506.39 Kb.


ABSTRACT

Pulmonary tuberculosis (TB) is a public health problem worldwide. The World Health Organization estimated about 10 million sick people and 1.3 million deaths in 2017. The ability of MTB to modulate the immune response, survive and persist under the hostile environment in the host and in latent TB has been extensively investigated, and requires regulation and control of genetic expression. The objective is to present a review of research related to regulators of MTB gene expression that are associated with virulence, persistence and survival in latent TB. A review of the investigations of the last 20 years was made. Finally, it is concluded that MTB has a genetic machinery that controls the expression of genes that participate in virulence and persistence in response to hypoxia, oxidative stress, lack of nutrients and acidic pH. Among them, two-component systems, sigma factors and transcriptional regulators participate. It has been proven that they work interconnected as a network in some cases. The research findings provide insights for the discovery of new targets for the development of anti-tuberculosis drugs, new vaccines and methods for diagnosis of TB, with the purpose of providing new strategies for disease control.


REFERENCES

  1. World Health Organization. Global tuberculosis report 2018. Geneva: WHO; 2019. Disponible en: https://www.who.int/tb/publications/global_report/en/ (Consultado en línea: 27 de Julio del 2019).

  2. Bańuls AL, Sanou A, Van Ah N, Godreuil S. Mycobacterium tuberculosis: Ecology and evolution of a human bacterium. J of Med Microbiol. 2015;64:1261-9.

  3. Serafino-Wania RL. Tuberculosis 2: Pathophysiology and microbiology of pulmonary tuberculosis. SSMJ. 2013;6 (1):10-2.

  4. Prozorov A, Fedorova I, Bekker B, Danilenko B. The virulence factors of Mycobacterium tuberculosis: Genetic control, new conceptions. Rus J Gen. 2014;50(8):775-97.

  5. Voss G, Casimiro D, Neyrolles O, Williams A, Kaufmann S, McShane H, et al. Progress and challenges in TB vaccine development. F1000Res. 2018;7:199. doi: 10.12688/f1000research.13588.1 (Consultado en línea: 15 de Mayo del 2019).

  6. Sachdeva P, Misra R, Tyagi AK, Singh Y. The sigma factors of Mycobacterium tuberculosis: regulation of the regulators. FEBS J. 2010;277:605-26.

  7. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998;393:537-44.

  8. Fontalvo D, Gómez D. Genes de Mycobacterium tuberculosis involucrados en la patogenicidad y resistencia a antibióticos durante la tuberculosis pulmonar y extrapulmonar. MÉD. UIS. 2015;28(1):39-51. Disponible en: http://www.scielo.org.co/pdf/muis/v28n1/v28n1a04.pdf (Consultado en línea: 15 de Mayo del 2019).

  9. Borrero R, Álvarez N, Reyes F, Sarmiento ME, Acosta A. Mycobacterium tuberculosis: factores de virulencia. VacciMonitor 2011;20(1):34-38. Disponible en: http://scielo.sld.cu/pdf/vac/v20n1/vac06111.pdf (Consultado en línea: 25 de Julio del 2019).

  10. Smith I. Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence. Clin Microbiol Rev. 2003;16 (3):463-96.

  11. Ciu Huag L, Haiying L, Baoxue G. Innate immunity in tuberculosis: host defense vs pathogen evasión. Cell & Mol Immunol. 2017;14:963-75.

  12. Lerner TR, Borel S, Gutierrez MG. The innate immune response in human tuberculosis. Cell Microbiol. 2015; 17:1277-85.

  13. Maertzdorf J, Tönnies M, Lozza L, Schommer-Leitner S, Mollenkopf H, Torsten T, et al. Mycobacterium tuberculosis invasion of the human lung: First contact. Front. Immunol. 2018;9:1346. doi: 10.3389/fimmu.2018.01346 (Consultado en línea: 28 de Julio del 2019).

  14. Guirado E, Schlesinger LS. Modeling the Mycobacterium tuberculosis granuloma-The critical battlefield in host immunity and disease. Front. Immunol. 2013;4:98. doi: 10.3389/fimmu.2013.00098 (Consultado en línea: 27 de Julio del 2019).

  15. Walburger A, Koul A, Ferrari G, Nguyen L, Prescianotto-Baschong C, Huygen K, et al. Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Science 2004;304:1800-4.

  16. Wong D, Chao JD, Av-Gay Y. Mycobacterium tuberculosis-secreted phosphatases: From pathogenesis to targets for TB drug development. Trends Microbiol. 2013;21(2):100-9.

  17. Augenstreich J, Arbues A, Simeone R, Haanappel E, Wegener A, Sayes F, et al. ESX-1 and phthiocerol dimycocerosates of Mycobacterium tuberculosis act in concert to cause phagosomal rupture and host cell apoptosis. Cell Microbiol. 2017;19(7):e12726. doi: 10.1111/cmi.12726 (Consultado en línea: 27 de Julio del 2019).

  18. Nieto LM, Mehaffy C, Creissen E, Troudt J, Troy A, Bielefeldt-Ohmann H, et al. Virulence of Mycobacterium tuberculosis after acquisition of isoniazid resistance: Individual Nature of katG mutants and the possible role of AhpC. PLoS ONE 2016;11(11):e0166807. doi: 10.1371/journal.pone.0166807 (Consultado en línea: 10 de Junio del 2019).

  19. Danelishvili L, Yamazaki Y, Selker J, Bermudez LE. Secreted Mycobacterium tuberculosis Rv3654c and Rv3655c proteins participate in the suppression of macrophage apoptosis. PLoS ONE 2010;5(5):e10474. doi: 10.1371/journal.pone.0010474 (Consultado en línea: 5 de Mayo del 2019).

  20. Miller JL, Velmurugan K, Cowan MJ, Briken V. The type I NADH dehydrogenase of Mycobacterium tuberculosis counters phagosomal NOX2 activity to inhibit TNF-alpha-mediated host cell apoptosis. PLoS Pathog. 2010;6 (4):e1000864. doi: 10.1371/journal.ppat.1000864 (Consultado en línea: 30 de Mayo del 2019).

  21. Chandra P, Ghanwat S, Kumar-Matta S, Seth-Yadav S, Mehta M, Siddiqui Z, et al. Mycobacterium tuberculosis inhibits RAB7 recruitment to selectively modulate autophagy flux in macrophages. Sci Rep. 2015;5:16320. doi: 10.1038/srep16320 (Consultado en línea: 2 de Abril del 2019).

  22. McKinney J, Höner K, Muńoz E, Mlczak A, Cheng B, Swenson D, et al. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 2000;406:435-8.

  23. Zhou P, Long Q, Zhou Y, Wang H, Xie J. Mycobacterium tuberculosis two-component systems and implications in novel vaccines and drugs. Crit Rev Eukaryot Gene Expr. 2012;22(1):37-52.

  24. Goyal R, Das AK, Singh R, Singh PK, Korpole S, Sarkar D. Phosphorylation of PhoP protein plays direct regulatory role in lipid biosynthesis of Mycobacterium tuberculosis. J Biol Chem. 2011;286:45197-208. doi: 10.1074/jbc.M111.307447 (Consultado en línea: 15 de Julio del 2019).

  25. Walters SB. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006;60:312-30.

  26. Pérez E, Samper S, Bordas Y, Guilhot C, Gicquel B, Martín C. An essential role for phoP in Mycobacterium tuberculosis virulence. Mol. Microbiol. 2001;41:179-87.

  27. Gonzalo-Asensio J, Mostowy S, Harders-Westerveen J, Huygen K, Hernández-Pando R, Thole J, et al. PhoP: a missing piece in the intricate puzzle of Mycobacterium tuberculosis virulence. PLoS ONE 2008;3(10):e3496. doi: 10.1371/journal.pone.0003496 (Consultado en línea: 4 de Julio del 2019).

  28. Walters SB. The Mycobacterium tuberculosis PhoPR two-component system regulates genes essential for virulence and complex lipid biosynthesis. Mol. Microbiol. 2006;60:312-30.

  29. Gonzalo-Asensio J. The virulence-associated two-component PhoP-PhoR system controls the biosynthesis of polyketide-derived lipids in Mycobacterium tuberculosis. J Biol Chem. 2006;281:1313-6.

  30. Ludwiczak P, Gilleron M, Bordat Y, Martin C, Gicquel B, Puzo G. Mycobacterium tuberculosis phoP mutant: lipoarabinomannan molecular structure. Microbiol. 2002;148:3029-37.

  31. Nigou J, Puzo G, Olivier M. Mannosylated lipoarabinomannan antagonize Mycobacterium tuberculosis-induced macrophage apoptosis by altering Ca+2-dependent cell signaling. J Infect Dis. 2000;182:240-51.

  32. Boon C, Dick T. How Mycobacterium tuberculosis goes to sleep: the dormancy survival regulator DosR a decade later. Future Microbiol. 2012;7:513-8.

  33. De Majumdar S, Vashist A, Dhingra S, Gupta D, Singh D, Vijay K, et al. Appropriate DevR (DosR)-Mediated Signaling Determines Transcriptional Response, Hypoxic Viability and Virulence of Mycobacterium tuberculosis. PLoS ONE 2012;7(4):e35847. doi: 10.1371/journal.pone.0035847 (Consultado en línea: 3 de Agosto del 2019).

  34. Parish T, Smith D, Kendall S, Casali N, Bancroft G, Stoker N. Deletion of Two-Component Regulatory Systems Increases the Virulence of Mycobacterium tuberculosis. Infect and Immun. 2003;71(3):1134-40.

  35. Smriti M, Foreman T, Didier P, Ahsan M, Hudock T, Kissee R, et al. The DosR Regulon Modulates Adaptive Immunity and Is Essential for Mycobacterium tuberculosis Persistence. Am J Respir Crit Care Med 2015;191(10):1185-96.

  36. Gautam U, McGillivray A, Smriti M, Didier P, Midkiff C, Kissee R. DosS Is Required for the Complete Virulence of Mycobacterium tuberculosis in Mice with Classical Granulomatous Lesions. Am J of Resp Cell and Mol Biol 2015;52(6):708-16.

  37. Parish T, Smith DA, Roberts G, Betts J, Stoker NG. The senX3-regX3 two-component regulatory system of Mycobacterium tuberculosis is required for virulence. Microbiol. 2003;149:1423-35.

  38. Rifat D, Bishai WR, Karakousis PC. Phosphate depletion: a novel trigger for Mycobacterium tuberculosis persistence. J Inf Dis 2009;200:1126-35.

  39. Rifat D, Karakousis P. Differential regulation of the two-component regulatory system senX3-regX3 in Mycobacterium tuberculosis. Microbiol 2014;160:1125-33.

  40. Tischler A, Leistikow D, Kirksey R, Voskuil MI, McKinney J. Mycobacterium tuberculosis requires phosphate-responsive gene regulation to resist host immunity. Infect Immun. 2013;81:317-28.

  41. Singh N, Kumar A. Virulence Factor SenX3 Is the oxygen-controlled replication switch of Mycobacterium tuberculosis. Antioxid Redox Signal 2015;22(7):603-13.

  42. Frota C, Papavinasasundaram K, Davis K, Colston M. The AraC Family Transcriptional Regulator Rv1931c Plays a Role in the Virulence of Mycobacterium tuberculosis. Infect and Immun. 2004;72(9):5483-6.

  43. Singh A, Gupta R, Vishwakarma RA, Narayanan PR, Paramasivan CN, Ramanathan VD, et al. Requirement of the mymA operon for appropriate cell Wall ultrastructure and persistence of Mycobacterium tuberculosis in the spleens of guinea pigs. J Bacteriol. 2005;187:4173-86.

  44. Cheruvu M, Plikaytis BB, Shinnick TM. The acid induced operon Rv3083-Rv3089 is required for growth of Mycobacterium tuberculosis in macrophages. Tuberculosis 2007;87(1):12-20.

  45. Zheng F, Long Q, Xie J. The function and regulatory network of WhiB and WhiB-like protein from comparative genomics and systems biology perspectives. Cell Biochem Biophys. 2012;63(2):103-8.

  46. Larsson C, Luna B, Ammerman N, Maiga M, Agarwal N, and Bishai W. Gene expression of Mycobacterium tuberculosis putative transcription factors whiB1-7 in redox environments. PLoS ONE 2012;7(7):e37516. doi: 10.1371/journal.pone.0037516 (Consultado en línea: 20 de Agosto del 2019).

  47. Singh A, Crossman DK, Mai D, Guidry L, Voskuil MI, Renfrow MB, et al. Mycobacterium tuberculosis WhiB3 maintains redox homeostasis by regulating virulence lipid anabolism to modulate macrophage response. PLoS Pathog. 2009;5(8):e1000545. doi: 10.1371/journal.ppat.1000545 (Consultado en línea: 30 de abril de 2019).

  48. Manganelli R. Sigma factors: key molecules in Mycobacterium tuberculosis physiology and virulence. Microbiol Spectr. 2014;2(1):MGM2-0007-2013. doi: 10.1128/microbiolspec.MGM2-0007-2013 (Consultado en línea: 30 de Mayo del 2019).

  49. Steyn AJ, Collins DM, Hondalus MK, Jacobs WR Jr, Kawakami RP, Bloom BR. Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth. Proc Natl Acad Sci USA. 2002;99(5):3147-52.

  50. Wu S, Howard ST, Lakey DL, Kipnis A, Samten B, Safi H, et al. The principal sigma factor SigA mediates enhanced growth of Mycobacterium tuberculosis in vivo. Mol Microbiol. 2004;51:1551-62.

  51. Fontan PA, Voskuil MI, Gómez M, Tan D, Pardini M, Manganelli R, et al. The Mycobacterium tuberculosis sigma factor SigB is required for full response to cell envelope stress and hypoxia in vitro, but it is dispensable for in vivo growth. J Bacteriol. 2009;191:5628-33.

  52. Abdul-Majid KB, Ly LH, Converse PJ, Geiman DE, McMurray DN, Bishai WR. Altered cellular infiltration and cytokine levels during early Mycobacterium tuberculosis sigC mutant infection are associated with late-stage disease attenuation and milder immunopathology in mice. BMC Microbiol. 2008;8(1):151-62.

  53. Karls RK, Guarner J, McMurray DN, Birkness KA, Quinn FD. Examination of Mycobacterium tuberculosis sigma factor mutants using low-dose aerosol infection of guinea pigs suggests a role for SigC in pathogenesis. Microbiol. 2006;152:1591-600.

  54. Manganelli R, Fattorini L, Tan D, Iona E, Orefici G, Altavilla G, et al. The extra cytoplasmic function sigma factor E is essential for Mycobacterium tuberculosis virulence in mice. Infect. Immun. 2004;72(5):3038-41.

  55. Manganelli R, Voskuil M, Schoolink GK, Smith H. The Mycobacterium tuberculosis ECF sigma factor σE : role in global gene expression and survival in macrophages. Mol Microbiol. 2001;41(2):423-37.

  56. Kaushal D, Schroeder B, Tyagi S, Yoshimatsu T, Scott C, Ko C, et al. Reduced immunopathology and mortality despite tissue persistence in a Mycobacterium tuberculosis mutant lacking alternative factor, SigH. PNAS 2002;99(12):8330-5.

  57. Capuano S, Croix DA, Pawar S, ZinoviK A, Myers A, Lin P, et al. Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of humans M. tuberculosis infections. Infect. Immun. 2003;71:5831-44




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