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

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

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.

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Main Authors: Matsui,Tania, Pinhata,Juliana Maíra Watanabe, Rabello,Michelle Christiane da Silva, Brandão,Angela Pires, Ferrazoli,Lucilaine, Leão,Sylvia Cardoso, Viana-Niero,Cristina, Oliveira,Rosangela Siqueira de
Format: Digital revista
Language:English
Published: Instituto Oswaldo Cruz, Ministério da Saúde 2020
Online Access:http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762020000100315
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spelling oai:scielo:S0074-027620200001003152020-04-28Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, BrazilMatsui,TaniaPinhata,Juliana Maíra WatanabeRabello,Michelle Christiane da SilvaBrandão,Angela PiresFerrazoli,LucilaineLeão,Sylvia CardosoViana-Niero,CristinaOliveira,Rosangela Siqueira de MDR-TB pre-XDR-TB XDR-TB gyrA gyrB rrs 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.info:eu-repo/semantics/openAccessInstituto Oswaldo Cruz, Ministério da SaúdeMemórias do Instituto Oswaldo Cruz v.115 20202020-01-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762020000100315en10.1590/0074-02760200055
institution SCIELO
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country Brasil
countrycode BR
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libraryname SciELO
language English
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author Matsui,Tania
Pinhata,Juliana Maíra Watanabe
Rabello,Michelle Christiane da Silva
Brandão,Angela Pires
Ferrazoli,Lucilaine
Leão,Sylvia Cardoso
Viana-Niero,Cristina
Oliveira,Rosangela Siqueira de
spellingShingle Matsui,Tania
Pinhata,Juliana Maíra Watanabe
Rabello,Michelle Christiane da Silva
Brandão,Angela Pires
Ferrazoli,Lucilaine
Leão,Sylvia Cardoso
Viana-Niero,Cristina
Oliveira,Rosangela Siqueira de
Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, Brazil
author_facet Matsui,Tania
Pinhata,Juliana Maíra Watanabe
Rabello,Michelle Christiane da Silva
Brandão,Angela Pires
Ferrazoli,Lucilaine
Leão,Sylvia Cardoso
Viana-Niero,Cristina
Oliveira,Rosangela Siqueira de
author_sort Matsui,Tania
title Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, Brazil
title_short Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, Brazil
title_full Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, Brazil
title_fullStr Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, Brazil
title_full_unstemmed Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, Brazil
title_sort frequency of first and second-line drug resistance-associated mutations among resistant mycobacterium tuberculosis clinical isolates from são paulo, brazil
description 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.
publisher Instituto Oswaldo Cruz, Ministério da Saúde
publishDate 2020
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762020000100315
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