• José Wellington Macêdo Viana Universidade Federal do Cariri - UFCA
  • Rodolfo Pinheiro Torres Universidade Federal do Piauí - UFPI



Tuberculosis (TB) is a chronic and serious infectious disease caused by Mycobacterium tuberculosis that mainly affects the lungs, but it is also capable of infecting other organs/tissues in the body, which triggers extra-pulmonary TB. In recent years, there has been an increase in the number of re-emerging TB cases due to resistance of M. tuberculosis to the antibiotics used to treat this disease. On top of that, there is the emergence of multidrug-resistant M. tuberculosis for which many of the antibiotics previously used have no effect. For these reasons, it was aimed to investigate the resistance mechanisms of M. tuberculosis in the TB pathogenicity in humans, considering this as a factor associated with re-emergence cases of this disease. Thus, it was carried out an integrative literature review based on articles selected in the SciElo, PubMed and Science Direct databases by using terminology in Portuguese and in English. Studies highlighted that the resistance mechanisms of M. tuberculosis consist of the emergence of mutations in target-genes naturally selected over time, the presence of efflux pumps and some lipid substances in the bacterial cell wall that provide impermeability to the antibiotics with cytoplasmic activity. Furthermore, the inappropriate use of antibiotics during the antibiotic-therapy period causes the emergence of other types of resistance. Therefore, special attention must be given to the correct use of antibiotics during the TB treatment, as well as the development of new effective drugs against multidrug-resistant bacteria strains.

Biografia do Autor

José Wellington Macêdo Viana, Universidade Federal do Cariri - UFCA

Departamento de Ciências Biológicas.

Biologia Geral e Biologia Molecular.

Rodolfo Pinheiro Torres, Universidade Federal do Piauí - UFPI

Graduando de Licenciatura em Letras Inglês e Literatura de Língua Inglesa - UFPI. Ex-professor Bolsista do programa Rede ANDIFES Idiomas Sem Fronteiras - UFPI 2018-2021. Pesquisador na área de linguística aplicada. Atualmente professor de inglês na sede Audir Lages SENAC Teresina,Pi.


ALMEIDA P. E. S.; PALOMINO J. C. Molecular basis and mechanisms of drug resistance in Mycobacterium tuberculosis: classical and new drugs. Journal of Antimicrobial Chemotherapy, v. 66, n. 7, p. 1417-30, 2011. DOI: 10.1093/jac/dkr173.

ALÓS, J. I. Antibiotic resistance: a global crisis. Enfermedades Infecciosas y Microbiologia Clínica, v. 33, n. 10, p. 692-699, 2015. DOI: 10.1016/j.eimc.2014.10.004.

BAILO, R.; BHATT, A.; AÍNSA, J. A. Lipid transport in Mycobacterium tuberculosis and its implications in virulence and drug development. Biochemical Pharmacology, v. 96, n. 3, p. 159-167, 2015. DOI: 10.1016/j.bcp.2015.05.001.

BALGANESH, M. et al. Efflux pumps of Mycobacterium tuberculosis play a significant role in anti-tuberculosis activity of potential drug candidates. Antimicrobial Agents in Chemotherapy, v. 56, p. 2643-2651, 2012. DOI:

BURIAN, J. et al. The mycobacterial transcriptional regulator whiB7 gene links redox homeostasis and intrinsic antibiotic resistance. Journal of Biological Chemistry, v. 287, p. 299-310, 2012. DOI:

CAMPOS, H. S. Mycobacterium tuberculosis resistente: de onde vem a resistência? Boletim de Pneumologia Sanitária, v. 7, n. 1. p. 52 -64, 2009.

CAMPOS, H. S. Tuberculose: etiopatogênese e apresentações clínicas. Pulmão, v. 15, n. 1, p. 29-35, 2006.

DA COSTA, A. L. P.; JÚNIOR, A. C. S. S. Resistência bacteriana aos antibióticos e Saúde Pública: uma breve revisão de literatura. Estação Científica (UNIFAP), v. 7, n. 2, p. 45-57, 2017. DOI: 10.18468.

DA SILVA; R. R.; LYRA, T. M.; CHAVES, A. M. Perfil epidemiológico dos abandonos de tuberculose em uma Capital do Nordeste do Brasil. Revista Interfaces: Saúde, Humanas e Tecnologia, v. 9, n. 2, p. 1072-1077, 2021. DOI:

DA SILVA, H. R. et al. Reflexo do desequilíbrio ambiental na saúde: bactérias multirresistentes em ambiente hospitalar. Research, Society and Development, v. 9, n. 8, e220985604, 2020. DOI:

DE LOUREIRO MAIOR, M.; GUERRA, R. L.; CAILLEAUX-CEZAR, M.; GOLUB, J. E.; CONDE, M. B. Time from symptom onset to the initiation of treatment of pulmonary tuberculosis in a city with a high incidence of the disease. Brasilian Journal of Pneumology, v. 38, n. 2, p. 202-209, 2012. DOI: 10.1590/s1806-37132012000200009.

FERRI, A. O. et al. Diagnóstico da tuberculose: uma revisão. Revista Liberato, v. 15, n. 24, p. 105-212, 2014.

FURTADO, D. M. F; SILVEIRA, V. D. da.; CARNEIRO, I. C. do R. S.; FURTADO, D. M. F.; KILISHEK, M. P. Consumo de antimicrobianos e o impacto na resistência bacteriana em um hospital público do estado do Pará, Brasil, de 2012 a 2016. Revista Pan-Amazônica de Saúde, v. 10, e201900041, 2019.

GEIMAN, D. E.; RAGHUNAND, T. R.; AGARWAL, N.; BISHAI, W. R. Differential gene expression in response to exposure to antimycobacterial agents and other stress conditions among seven Mycobacterium tuberculosis whiB-like genes. Antimicrobial Agents and Chemotherapy, v. 50, p. 2836-2841, 2016. DOI:

GOMEZ, J. E.; McKINNEY, J. D. Mycobacterium tuberculosis persistence, latency, and drug tolerance. Tuberculosis, v. 84, n. 1-2, p. 29-44, 2014. DOI: 10.1016/

GÓMEZ-TANGARIFE, J. V.; GÓMEZ-RESTREPO, A. J.; ROBLEDO-RESTREPO, J.; HERNÁNDEZ-SARMIENTO, J. M. Drug resistance in Mycobacterium tuberculosis: contribution of constituent and acquired mechanisms. Revista de Salud Pública, v. 20, n. 4, p. 491-497, 2018. DOI: 10.15446/rsap.V20n4.50575.

GOOSSENS, S. N.; SAMPSON, S. L.; VAN RIE, A. Mechanisms of drug-induced tolerance in Mycobacterium tuberculosis. Clinical Microbiology Reviews, v. 34, n. 1, 2020. DOI: 10.1128/CMR.00141-20.

GURGEL, T. C.; CARVALHO, W. S. A Assistência Farmacêutica e o Aumento da Resistência Bacteriana aos Antibióticos. Latin American Journal of Pharmacy, v. 27, n. 1, p. 118-123, 2018. ISSN 0326-2383.

GYGLI, S. M.; BORREL, S.; TRAUNER, A.; GAGNEUX, S. Antimicrobial resistance in Mycobacterium tuberculosis: mechanistic and evolutionary perspectives. FEMS Microbiology Reviews, v. 41, n. 3, p. 354-373, 2017. DOI: 10.1093/femsre/fux011

HUSSELL, T.; BELL, T. J. Alveolar macrophages: plasticity in a tissue-specific context. Nature Reviews Immunology, v. 14, p. 81–93, 2014. DOI: 10.1038/nri3600.

KARAKOUSIS, P. C.; WILLIAMS, E. P.; BISHAI, W. R. Altered expression of isoniazid-regulated genes in drug-treated dormant Mycobacterium tuberculosis. Journal of Antimicrobial Chemotherapy, v. 61, n. 2, p. 323-31, 2008. DOI: 10.1093/jac/dkm485.

KHAWBUNG, J. L.; NATH, D.; CHAKRABORTY, S. Drug resistant Tuberculosis: A review. Comparative Immunology, Microbiology and Infectious Diseases, 74, e101574, 2021. DOI: https://doi:10.1016/j.cimid.2020.101574.

LAPAUSA, M. R.; PAREJA, J. F. P.; ASENSIO, A. N. New tuberculosis drugs in resistant and multi-resistant tuberculosis. Medicina Clínica – Journal Elsevier (Barc), v. 141, n. 7, p. 306-313, 2013. DOI: 10.1016/j.medcli.2013.01.039.

LI, G. et al. Efflux pump gene expression in multidrug-resistant Mycobacterium tuberculosis clinical isolates. PLoS One, v. 10, e0119013, 2015. DOI:

LOUW, G. E. et al. Rifampicin reduces susceptibility to ofloxacin in rifampicin-resistant Mycobacterium tuberculosis through efflux. American Journal of Respiratory and Critical Care Medicine, v. 184, p. 269-276, 2011. DOI:

MARTINSON, N. A. et al. New regimens to prevent Tuberculosis in adults with HIV infection. The New England Journal of Medicine, v. 365, n. 1, p. 11-20, 2011.

MORRIS, R. P. et al. Ancestral antibiotic resistance in Mycobacterium tuberculosis. Proceedings of National Academy of Sciences, v. 102, n. 34, p. 12200-12205, 2015. DOI: 10.1073/pnas.0505446102.

MORTAZ, E. et al. Interaction of pattern recognition receptors with Mycobacterium tuberculosis. Journal of Clinical Immunology, v. 35, p. 01–10, 2015. DOI: 10.1007/s10875-014-0103-7.

MOTA, L. M.; VILAR, F. C.; DIAS, L. B. A.; NUNES, T. F.; MORIGUTI, J. C. Uso racional de antimicrobianos. Medicina, v. 43, n. 2, p.164-172, 2010. DOI:

MOUTINHO, I. L. D. Tuberculose: aspectos imunológicos na infecção e na doença. Revista de Medicina de Minas Gerais, v. 21, n. 1, p. 42-48, 2011.

NAHID, P. et al. Executive Summary - Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug Susceptible Tuberculosis. Clinical and Infectious Diseases, v. 63, n. 7, p. 853-67, 2016.

NETO, J. C. et al. Review of the medicinal use of Rhaphiodon echinus Schauer (Lamiaceae): biological and pharmacological activities. Research, Society and Development, v. 10, n. 3, p. 01-12, 2021. DOI:

NGUYEN, L. Antibiotic resistance mechanisms in M. tuberculosis: an update. Archives in Toxicology, v. 90, p. 1585–1604, 2016. DOI:

NOGUEIRA, A. F.; FACCHINETTI, V.; SOUZA, M. V. N. de.; VASCONCELOS, T. R. A. Tuberculose: uma abordagem geral dos principais aspectos. Revista Brasileira de Farmácia, v. 93, n. 1, p. 3-9, 2012.

PEDRAZZOLI, D.; KRANZER, K.; THOMAS, H. L.; LALOR, M. K. Trends and risk factors for death and excess all-cause mortality among notified tuberculosis patients in the UK: an analysis of surveillance data. ERJ Open Research, v. 5, n. 4, p. 00125–2019, 2019. DOI: 10.1183/23120541.00125-2019.

RABAHI, M. F.; JÚNIOR, J. L. R. S.; FERREIRA, A. C. G.; TANNUS-SILVA, D. G. S.; CONDE, M. B. Tratamento da tuberculose. Revista Brasileira de Pneumologia, v. 43, n. 5, p. 472-486, 2017. DOI:

ROSSETTI, M. R. L.; VALIM, A. R. M.; SILVA, M. S. N.; RODRIGUES, V. S. Resistant tuberculosis: a molecular review. Journal of Public Health, v. 36, n. 4, p. 525-532, 2012. DOI: 10.1590/s0034-89102002000400021.

SAMANDARI, T et al. 6-Month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomized, double-blind placebo-controlled trial. Lancet, v. 377, p. 1588-1598, 2011.

SCHÖN, T. et al. Mycobacterium tuberculosis drug-resistance testing: challenges, recent developments and perspectives. Clinical Microbiology and Infection, v. 23, n. 3, p. 154-160, 2017. DOI: 10.1016/j.cmi.2016.10.022.

SIMMONS, J. D. et al. Immunological mechanisms of human resistance to persistent Mycobacterium tuberculosis infection. Nature Reviews Immunology, v. 18, n. 9, p. 575-589, 2018. DOI: 10.1038/s41577-018-0025-3.

SINGH, R. et al. Recent updates on drug resistance in Mycobacterium tuberculosis. Journal of Applied Microbiology, v. 128, n. 6, p. 1547-1567, 2019. DOI: 10.1111/jam.14478.

SIQUEIRA, C. M. M. Resistência aos Antibióticos: O uso inadequado dos antibióticos na prática clínica. Resista de la Organización de Farmacéuticos Iberoamericanos, v. 14, n. 1, p. 45-68, 2016.

STAMM, C. E.; COLLINS, A. C.; SHILOH, M. U. Sensing of Mycobacterium tuberculosis and consequences to both host and bacillus. Immunological Reviews, v. 264, p. 204–219, 2015. DOI: 10.1111/imr.12263.

SZUMOWSKI, J. D.; ADAMS, K. N.; EDELSTEIN, P. H.; RAMAKRISHNAN, L. Antimicrobial efflux pumps and Mycobacterium tuberculosis drug tolerance: evolutionary considerations. Current Topics in Microbiology and Immunology, v. 374 p. 81–108, 2013. DOI:

TORRELLES, J. B.; SCHLESINGER, L. S. Integrating lung physiology, immunology, and tuberculosis. Trends in Microbiology, v. 25, p. 688–697, 2017. DOI: 10.1016/j.tim.2017.03.007.

WALTER, N. D. et al. Transcriptional adaptation of drug-tolerant Mycobacterium tuberculosis during treatment of human tuberculosis. Journal of Infectious Diseases, v. 212, p. 990-998, 2015. DOI:

WEISS, G.; SCHAIBLE, U. E. Macrophage defense mechanisms against intracellular bacteria. Immunological Reviews, v. 264, n. 1, p. 182–203, 2015. DOI: 10.1111/imr.12266.

WORLD HEALTH ORGANIZATION (WHO). Tuberculosis (TB). Available on: Access on: December, 22th, 2021.

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 Biochemistry and Biophysics, v. 63, p. 103–108, 2012. DOI: 10.1007/s12013-012-9348-z.