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Article

Whole-Genome Sequence Analysis to Assess Mutations in Efflux Pumps in Mycobacterium tuberculosis: The Influence in Drug Resistance

by
Miguel Chimal-Muñoz
1,
Damián E. Pérez-Martínez
1,
Gustavo A. Bermúdez Hernández
2,
Paulina M. Mejía-Ponce
3,
Cuauhtémoc Licona-Cassani
3,4,5,
Raquel Muñiz-Salazar
4,6,
Hilda Montero
2 and
Roberto Zenteno-Cuevas
2,4,*
1
Health Sciences Doctoral Program, Instituto de Ciencias de la Salud, Universidad Veracruzana, Veracruz 91190, Mexico
2
Instituto de Salud Pública, Universidad Veracruzana, Av. Luis Castelazo Ayala s/n, A.P. 57 Col. Industrial Animas, Veracruz 91190, Mexico
3
Escuela de Ingeniería y Ciencias, Tecnológico de Monterrey, Monterrey 64849, Mexico
4
Red Multidisciplinaria de Investigación en Tuberculosis, Ensenada 22890, Mexico
5
Division of Integrative Biology, The Institute for Obesity Research, Tecnológico de Monterrey, Monterrey 64849, Mexico
6
Escuela de Ciencias de la Salud, Universidad Autónoma de Baja California, Ensenada 22890, Mexico
*
Author to whom correspondence should be addressed.
Microorganisms 2025, 13(6), 1306; https://doi.org/10.3390/microorganisms13061306
Submission received: 27 January 2025 / Revised: 25 May 2025 / Accepted: 27 May 2025 / Published: 4 June 2025
(This article belongs to the Special Issue Prevention, Treatment and Diagnosis of Tuberculosis, 2nd Edition)

Abstract

Efflux pumps are proteins related to the transport of molecules in bacteria, and some of them have been recently reported to be involved in drug resistance (DR) in Mycobacterium tuberculosis. In addition, the association with type 2 diabetes mellitus (T2DM) has been considered a factor favoring the development of drug resistance. Therefore, the aim of this study was to characterize, by analysis of M. tuberculosis genomes, the variants in efflux pump genes and to determine the level of association with T2DM and DR. Nearly 400 Mtb genomes from individuals with and without T2DM and with and without DR were recovered. Of the 164 efflux pump genes analyzed, 10 lack any variant, while 154 genes presented from 3 to 19 variants. The variant S217P in mmpL13a (Rv1145) was the most abundant, found in 98 (25%) isolates. A significant association was observed between 19 variants and DR, and between 20 variants and T2DM (p ≤ 0.005). Although preliminary, the results show a tendency for certain variants to appear in tuberculosis isolates from individuals with DR and T2DM, demonstrating the possible influence of the host in the evolution of tuberculosis. Further studies are necessary to confirm the participation of these variants in the efflux pump function in tuberculosis.
Keywords: tuberculosis; diabetes mellitus; resistance; efflux pumps tuberculosis; diabetes mellitus; resistance; efflux pumps

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MDPI and ACS Style

Chimal-Muñoz, M.; Pérez-Martínez, D.E.; Bermúdez Hernández, G.A.; Mejía-Ponce, P.M.; Licona-Cassani, C.; Muñiz-Salazar, R.; Montero, H.; Zenteno-Cuevas, R. Whole-Genome Sequence Analysis to Assess Mutations in Efflux Pumps in Mycobacterium tuberculosis: The Influence in Drug Resistance. Microorganisms 2025, 13, 1306. https://doi.org/10.3390/microorganisms13061306

AMA Style

Chimal-Muñoz M, Pérez-Martínez DE, Bermúdez Hernández GA, Mejía-Ponce PM, Licona-Cassani C, Muñiz-Salazar R, Montero H, Zenteno-Cuevas R. Whole-Genome Sequence Analysis to Assess Mutations in Efflux Pumps in Mycobacterium tuberculosis: The Influence in Drug Resistance. Microorganisms. 2025; 13(6):1306. https://doi.org/10.3390/microorganisms13061306

Chicago/Turabian Style

Chimal-Muñoz, Miguel, Damián E. Pérez-Martínez, Gustavo A. Bermúdez Hernández, Paulina M. Mejía-Ponce, Cuauhtémoc Licona-Cassani, Raquel Muñiz-Salazar, Hilda Montero, and Roberto Zenteno-Cuevas. 2025. "Whole-Genome Sequence Analysis to Assess Mutations in Efflux Pumps in Mycobacterium tuberculosis: The Influence in Drug Resistance" Microorganisms 13, no. 6: 1306. https://doi.org/10.3390/microorganisms13061306

APA Style

Chimal-Muñoz, M., Pérez-Martínez, D. E., Bermúdez Hernández, G. A., Mejía-Ponce, P. M., Licona-Cassani, C., Muñiz-Salazar, R., Montero, H., & Zenteno-Cuevas, R. (2025). Whole-Genome Sequence Analysis to Assess Mutations in Efflux Pumps in Mycobacterium tuberculosis: The Influence in Drug Resistance. Microorganisms, 13(6), 1306. https://doi.org/10.3390/microorganisms13061306

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