Whole genome sequencing reveals candidate genes involving in PAS resistance in M. Tuberculosis isolated from patients in Thailand.
World J Microbiol Biotechnol
; 40(1): 32, 2023 Dec 07.
Article
em En
| MEDLINE
| ID: mdl-38057660
ABSTRACT
Para-amino salicylic acid (PAS) was first reported by Lehmann in 1946 and used for tuberculosis treatment. However, due to its adverse effects, it is now used only as a second line anti-tuberculosis drug for treatment of multidrug resistant or extensively drug resistant M. tuberculosis. The structure of PAS is similar to para-amino benzoic acid (pABA), an intermediate metabolite in the folate synthesis pathway. The study has identified mutations in genes in folate pathway and their intergenic regions for their possibilities in responsible for PAS resistance. Genomic DNA from 120 PAS-resistant and 49 PAS-sensitive M. tuberculosis isolated from tuberculosis patients in Thailand were studied by whole genome sequencing. Twelve genes in the folate synthesis pathway were investigated for variants associated with PAS resistance. Fifty-one SNVs were found in nine genes and their intergenic regions (pabC, pabB, folC, ribD, thyX, dfrA, thyA, folK, folP). Functional correlation test confirmed mutations in RibD, ThyX, and ThyA are responsible for PAS resistance. Detection of mutation in thyA, folC, intergenic regions of thyX, ribD, and double deletion of thyA dfrA are proposed for determination of PAS resistant M. tuberculosis.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ácido Aminossalicílico
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Tuberculose
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Tuberculose Resistente a Múltiplos Medicamentos
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Mycobacterium tuberculosis
Limite:
Humans
País como assunto:
Asia
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article