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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.)

Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, Brazil

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Author(s):
Tania Matsui ; Juliana Maíra Watanabe Pinhata [2] ; Michelle Christiane da Silva Rabello [3] ; Angela Pires Brandão [4] ; Lucilaine Ferrazoli [5] ; Sylvia Cardoso Leão [6] ; Cristina Viana-Niero [7] ; Rosangela Siqueira de Oliveira [8]
Total Authors: 8
Document type: Journal article
Source: Memórias do Instituto Oswaldo Cruz; v. 115, 2020-05-08.
Abstract

BACKGROUND Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, and the number of new cases of multidrug resistant TB (MDR-TB), pre extensively drug-resistant TB (pre-XDR-TB) and extensively drug-resistant TB (XDR-TB) has increased considerably worldwide. OBJECTIVES Herein, using 156 M. tuberculosis isolates from 106 patients previously classified as MDR or pre-XDR or XDR isolates, we investigated the genetic mutation profiles associated with phenotypic resistances in patients with MDR-TB, pre-XDR-TB and XDR-TB, treatment outcomes and resistance evolution. METHODS Molecular analyses were performed by partial sequencing of the rpoB, katG, gyrA, gyrB, rrs genes and analysis of the fabG-inhA promoter region. Clinical, epidemiologic and demographic data were obtained from the TB Notification database system of São Paulo (TB-WEB) and the Information System for Special Tuberculosis Treatments (SITE-TB). FINDINGS Drug resistance was attributed to previously known mutations and a novel Asp449Val mutation in gyrB was observed in four isolates from the same patient. Ten patients had more than one isolate evaluated and eight of these patients displayed resistance progression. MAIN CONCLUSIONS The present study is the first to report the frequency of mutations related to second-line drug resistance in MDR-TB, pre-XDR-TB and XDR-TB isolates. The results could lead to the improvement of available technologies for the rapid detection of drug resistant TB. (AU)

FAPESP's process: 17/16082-7 - Characterization of mutations in clinical isolates of Mycobacterium tuberculosis resistant to 1st and 2nd line drugs and the relationship between mutations and phenotypic resistance levels to isoniazid.
Grantee:Rosangela Siqueira de Oliveira
Support Opportunities: Regular Research Grants