Mutations and insights into the molecular mechanisms of resistance of Mycobacterium tuberculosis to first-line

Autor(es)

Nicolas de Oliveira Rossini ^[1] ; Marcio Vinicius Bertacine Dias

Afiliação do(s) autor(es)

^[1] Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Microbiologia - Brasil

• Tipo de documento: Artigo Científico
• Fonte: GENETICS AND MOLECULAR BIOLOGY; v. 46, n. 1 2023-01-23.

Resumo

Abstract Genetically antimicrobial resistance in Mycobacterium tuberculosis is currently one of the most important aspects of tuberculosis, considering that there are emerging resistant strains for almost every known drug used for its treatment. There are multiple antimicrobials used for tuberculosis treatment, and the most effective ones are the first-line drugs, which include isoniazid, pyrazinamide, rifampicin, and ethambutol. In this context, understanding the mechanisms of action and resistance of these molecules is essential for proposing new therapies and strategies of treatment. Additionally, understanding how and where mutations arise conferring a resistance profile to the bacteria and their effect on bacterial metabolism is an important requisite to be taken in producing safer and less susceptible drugs to the emergence of resistance. In this review, we summarize the most recent literature regarding novel mutations reported between 2017 and 2022 and the advances in the molecular mechanisms of action and resistance against first-line drugs used in tuberculosis treatment, highlighting recent findings in pyrazinamide resistance involving PanD and, additionally, resistance-conferring mutations for novel drugs such as bedaquiline, pretomanid, delamanid and linezolid. (AU)

• Processo FAPESP: 19/17037-0 - Identificação de compostos que interagem com a MurE de Mycobacterium tuberculosis através da triagem de fragmentos
• Beneficiário: Nicolas de Oliveira Rossini
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 22/12234-5 - Resistência a antimicrobianos em Mycobacterium tuberculosis: análise estrutural, biofísica e bioquímica de mutações missense
• Beneficiário: Marcio Vinicius Bertacine Dias
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/03850-9 - Parede celular micobacteriana: estudo estrutural e estratégias de inibição de enzimas relacionadas com sua biossíntese e regulação
• Beneficiário: Marcio Vinicius Bertacine Dias
• Modalidade de apoio: Auxílio à Pesquisa - Regular