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Inicio Enfermedades Infecciosas y Microbiología Clínica (English Edition) rpoB, katG and inhA mutations in multi-drug resistant strains of Mycobacterium t...
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Vol. 37. Issue 5.
Pages 307-313 (May 2019)
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Vol. 37. Issue 5.
Pages 307-313 (May 2019)
Original article
DOI: 10.1016/j.eimce.2018.09.003
rpoB, katG and inhA mutations in multi-drug resistant strains of Mycobacterium tuberculosis clinical isolates from southeast Mexico
Mutaciones en rpoB, katG e inhA en cepas clínicas de Mycobacterium tuberculosis multi-farmacorresistentes del sureste de México
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Roberto Zenteno-Cuevasa,
Corresponding author
robzencue@gmail.com

Corresponding author.
, Betzaida Cuevas-Córdobab, Aurora Parissi-Crivellic
a Instituto de Salud Pública, Universidad Veracruzana, Veracruz, Mexico
b Departamento de Farmacogenómica, Instituto Nacional de Medicina Genómica, Mexico
c Laboratorio Estatal de Salud Pública, Servicios de Salud de Veracruz, Veracruz, Mexico
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Tables (4)
Table 1. Prevalence of drug resistance phenotypes among clinical multidrug resistant M. tuberculosis isolates (n=74).
Table 2. Mutations in the katG and inhA in MDR-TB isolates from Mexico, (n=74).
Table 3. Mutations in rpoB in MDR-TB isolates from Mexico (n=74).
Table 4. Combination of mutations and drug resistance profiles socio-demographic characteristics of MDR-TB isolates from Mexico.
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Abstract
Introduction

Previous knowledge of molecular mechanisms related with multi-drug resistances in tuberculosis is important if molecular diagnostic procedures want to be used in specific geographical regions. For that reason, the aim of this study was to investigate the mutations at rpoB, katG and inhA in multi-drug resistant tuberculosis isolates from Southeast Mexico.

Methods

Isolates of tuberculosis with a confirmed resistance against rifampicin and isoniazid were collected and sequencing analysis was performed of the rpoB rifampicin resistance-determining region, the katG and the encoding region of inhA.

Result

Of 74 isolates with multidrug resistance, 34 (46%) presented six mutations in katG; the most abundant was katG315 in 29 (39%) isolates. At inhA, nine (11%) isolates presented three mutations; the most frequent was inhA21, located in five (6%) strains. Eleven polymorphisms were observed at rpoB in 61 (82%) isolates, prevailing rpoB531 and rpoB 526 in 48 (64%) and ten (12%) isolates, respectively. Eleven double combinations were observed in 39 (52%) isolates, the most common of which was rpoB531+katG315, found in 22 (29%) strains.

Conclusion

This study provides valuable information on the diversity of polymorphisms in genes related to multidrug-resistant tuberculosis, as well as the presence of new mutations not previously described; this information should be considered in the implementation of molecular diagnostic tests.

Keywords:
Multidrug-resistance
Tuberculosis
rpoB
katG
inhA
Sequencing
Resumen
Introducción

El conocimiento previo de los mecanismos moleculares relacionados con las multi-farmacorresistencia es de suma importancia si se desean emplear procedimientos de diagnóstico molecular en regiones geográficas específicas. Por esa razón, el objetivo de este estudio fue investigar las mutaciones en rpoB, katG e inhA en cepas aisladas de tuberculosis multirresistente circulantes en el sureste de México.

Métodos

Se recuperaron aislados de tuberculosis con una resistencia confirmada a rifampicina e isoniazida, y se realizó la secuenciación y posterior análisis de la región determinante de la resistencia a rifampicina en el gen rpoB, así como del gen katG y la región codificante de inhA.

Resultado

De 74 cepas con multirresistencia, solo 34 (46%) presentaron 6 mutaciones en katG; la más abundante fue katG315 presente en 29 (39%) aislados. En inhA, solo 9 (11%) aislados presentaron 3 mutaciones; la más frecuente fue inhA21, localizada en 5 (6%) cepas. Se observaron en 61 (82%) cepas 11 polimorfismos en rpoB, siendo los más frecuentes rpoB531 en 48 (64%) y rpoB526 en 10 (12%) aislados, respectivamente. Se observaron 11 combinaciones dobles en 39 (52%) cepas, la más común fue rpoB531+katG315, presente en 22 (29%) cepas.

Conclusión

Este estudio proporciona información valiosa sobre la diversidad de polimorfismos en genes relacionados con la tuberculosis multirresistentes, así como la presencia de nuevas mutaciones no descritas previamente, esta información deberá ser considerar en la implementación de pruebas de diagnóstico molecular.

Palabras clave:
Multi-farmacorresistencia
Tuberculosis
rpoB
katG
inhA
Secuenciación

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