Whole Genome Sequencing Analysis to Evaluate the Influence of T2DM on Polymorphisms Associated with Drug Resistance in M. Tuberculosis

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2022 Jun 24

PMID 35751020

Authors

Gustavo Adolfo Bermudez-Hernandez

Damian Eduardo Perez-Martinez

Carlos Francisco Madrazo-Moya

Irving Cancino-Munoz

Inaki Comas

Roberto Zenteno-Cuevas

Affiliations

Soon will be listed here.

Abstract

Background: Type 2 diabetes mellitus (T2DM) has been associated with treatment failure, and the development of drug resistance in tuberculosis (TB). Also, whole-genome sequencing has provided a better understanding and allowed the growth of knowledge about polymorphisms in genes associated with drug resistance. Considering the above, this study analyzes genome sequences to evaluate the influence of type 2 diabetes mellitus in the development of mutations related to tuberculosis drug resistance. M. tuberculosis isolates from individuals with (n = 74), and without (n = 74) type 2 diabetes mellitus was recovered from online repositories, and further analyzed.

Results: The results showed the presence of 431 SNPs with similar proportions between diabetics, and non-diabetics individuals (48% vs. 52%), but with no significant relationship. A greater number of mutations associated with rifampicin resistance was observed in the T2DM-TB individuals (23.2% vs. 16%), and the exclusive presence of rpoBQ432L, rpoBQ432P, rpoBS441L, and rpoBH445L variants. While these variants are not private to T2DM-TB cases they are globally rare highlighting a potential role of T2DM. The phylogenetic analysis showed 12 sublineages, being 4.1.1.3, and 4.1.2.1 the most prevalent in T2DM-TB individuals but not differing from those most prevalent in their geographic location. Four clonal complexes were found, however, no significant relationship with T2DM was observed. Samples size and potential sampling biases prevented us to look for significant associations.

Conclusions: The occurrence of globally rare rifampicin variants identified only in isolates from individuals with T2DM could be due to the hyperglycemic environment within the host. Therefore, further studies about the dynamics of SNPs' generation associated with antibiotic resistance in patients with diabetes mellitus are necessary.

Citing Articles

Clinical and Mycobacterium tuberculosis strain characteristics of tuberculosis patients with diabetes mellitus in Changping District, Beijing, China.

Cao X, Song Z, He P, Li X, Lei N, Sun Q BMC Infect Dis. 2025; 25(1):101.

PMID: 39844060 PMC: 11753084. DOI: 10.1186/s12879-025-10470-z.

Association Between Diabetes Mellitus-Tuberculosis and the Generation of Drug Resistance.

Cornejo-Baez A, Zenteno-Cuevas R, Luna-Herrera J Microorganisms. 2025; 12(12.

PMID: 39770852 PMC: 11728438. DOI: 10.3390/microorganisms12122649.

Mutational Dynamics Related to Antibiotic Resistance in Isolates from Serial Samples of Patients with Tuberculosis and Type 2 Diabetes Mellitus.

Bermudez-Hernandez G, Perez-Martinez D, Ortiz-Leon M, Muniz-Salazar R, Licona-Cassani C, Zenteno-Cuevas R Microorganisms. 2024; 12(2).

PMID: 38399727 PMC: 10892438. DOI: 10.3390/microorganisms12020324.

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