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(Reference retrieved automatically from SciELO through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Nicolas de Oliveira Rossini [1] ; Marcio Vinicius Bertacine Dias
Total Authors: 2
Affiliation:
[1] Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Microbiologia - Brasil
Total Affiliations: 2
Document type: Journal article
Source: GENETICS AND MOLECULAR BIOLOGY; v. 46, n. 1 2023-01-23.
Abstract

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)

FAPESP's process: 19/17037-0 - Discovery of compounds that interact with MurE from Mycobacterium tuberculosis using fragment screening
Grantee:Nicolas de Oliveira Rossini
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 22/12234-5 - Resistance to antimicrobials in Mycobacterium tuberculosis: structural, biophysical and biochemical analysis of missense mutations
Grantee:Marcio Vinicius Bertacine Dias
Support Opportunities: Regular Research Grants
FAPESP's process: 20/03850-9 - Mycobacterium cell wall: structural studies and inhibition strategies for enzymes involved in the biosynthesis and regulation
Grantee:Marcio Vinicius Bertacine Dias
Support Opportunities: Regular Research Grants