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

Overview

Journal Microorganisms

Specialty Microbiology

Date 2024 Feb 24

PMID 38399727

Authors

Gustavo A Bermudez-Hernandez

Damian Perez-Martinez

Maria Cristina Ortiz-Leon

Raquel Muniz-Salazar

Cuauhtemoc Licona-Cassani

Roberto Zenteno-Cuevas

Affiliations

Soon will be listed here.

Abstract

Genetic variation in tuberculosis is influenced by the host environment, patients with comorbidity, and tuberculosis-type 2 diabetes mellitus (TB-T2DM) and implies a higher risk of treatment failure and development of drug resistance. Considering the above, this study aimed to evaluate the influence of T2DM on the dynamic of polymorphisms related to antibiotic resistance in TB. Fifty individuals with TB-T2DM and TB were initially characterized, and serial isolates of 29 of these individuals were recovered on day 0 (diagnosis), 30, and 60. Genomes were sequenced, variants related to phylogeny and drug resistance analyzed, and mutation rates calculated and compared between groups. Lineage X was predominant. At day 0 (collection), almost all isolates from the TB group were sensitive, apart from four isolates from the TB-T2DM group showing the mutation S315T, from which one isolate had the mutations S450L, A90G, and D94G. This pattern was observed in a second isolate at day 30. The results provide a first overview of the dynamics of mutations in resistance genes from individuals with TB-T2DM, describing an early development of resistance to isoniazid and a rapid evolution of resistance to other drugs. Although preliminary, these results help to explain the increased risk of drug resistance in individuals with TB and T2DM.

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