Characterization of Polymorphisms Associated with Multidrug-Resistant Tuberculosis by Whole Genomic Sequencing: A Preliminary Report from Mexico

Microb Drug Resist. 2020 Jul;26(7):732-740. doi: 10.1089/mdr.2019.0054. Epub 2019 Dec 23.

Abstract

Whole genome sequencing (WGS) has been proposed as a tool for the diagnosis of drug resistance in tuberculosis (TB); however, there have been few studies on its effectiveness in countries with significantly high drug resistance rates. This study therefore aimed to evaluate the effectiveness of WGS to identify mutations related to drug resistance in TB isolates from an endemic region of Mexico. The results showed that, of 35 multidrug-resistant isolates analyzed, the values of congruence found between the phenotypic drug susceptibility testing and polymorphisms were 94% for isoniazid, 97% for rifampicin, 90% for ethambutol, and 82% for pyrazinamide. It was also possible to identify eight isolates as potential pre-extensive drug resistant (XDR) and one as XDR. Twenty nine isolates were classified within L4 and two transmission clusters were identified. The results show the potential utility of WGS for predicting resistance against first- and second-line drugs, as well as providing a phylogenetic characterization of TB drug-resistant isolates circulating in Mexico.

Keywords: WGS; drug resistance; screening; tuberculosis.

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Extensively Drug-Resistant Tuberculosis / genetics
  • Humans
  • Mexico / epidemiology
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics*
  • Phenotype
  • Polymorphism, Genetic
  • Tuberculosis, Multidrug-Resistant / genetics*
  • Whole Genome Sequencing

Substances

  • Antitubercular Agents