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. OB...

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Bibliographic Details
Published in:Memórias do Instituto Oswaldo Cruz Vol. 115; p. e200055
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: Journal Article
Language:English
Published: Brazil Instituto Oswaldo Cruz, Ministério da Saúde 01-01-2020
Fundação Oswaldo Cruz (FIOCRUZ)
Subjects:
Adolescent
Adult
Antitubercular Agents - pharmacology
Brazil
Drug Resistance, Multiple, Bacterial - genetics
Extensively Drug-Resistant Tuberculosis - microbiology
Female
gyrA
gyrB
Humans
Male
MDR-TB
Microbial Sensitivity Tests
Middle Aged
Mutation - genetics
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - isolation & purification
Original
PARASITOLOGY
pre-XDR-TB
rrs
Socioeconomic Factors
TROPICAL MEDICINE
Tuberculosis, Multidrug-Resistant - microbiology
XDR-TB
Young Adult
Brazil
gyrA
MDR-TB
gyrB
rrs
XDR-TB
pre-XDR-TB
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Summary: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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CVN and RSO - Conceived the study and designed the experiments; TM, JMWP, APB, LF and MCSR - methodology; TM, LF, CVN and RSO - formal analysis; TM, JMWP, APB, MCSR, LF, SCL, CVN and RSO - writing-review and editing.
ISSN:0074-0276
1678-8060
1678-8060
DOI:10.1590/0074-02760200055