Genetic Diversity of Multi- and Extensively Drug-Resistant Mycobacterium tuberculosis Isolates in the Capital of Iran, Revealed by Whole-Genome Sequencing

J Clin Microbiol. 2019 Jan 2;57(1):e01477-18. doi: 10.1128/JCM.01477-18. Print 2019 Jan.

Abstract

The emergence and spread of multidrug resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains is a critical global health problem. Between 2014 and 2018, 606 MTBC strains were isolated from 13,892 suspected pulmonary tuberculosis (TB) patients in Tehran, Iran, including 16 (2.6%) MDR-TB cases. A combination of phenotypic and genotypic methods (whole-genome sequencing) was employed for the identification of additional drug resistances and strain-to-strain genetic distances as a marker for recent transmission events. MDR and extensively drug-resistant (XDR) TB cases were almost exclusively infected by lineage 2/Beijing strains (14/16, P < 0.001). We further showed that recent transmission and/or recent introduction of lineage 2/Beijing strains contribute to high XDR-TB rates among all MDR-TB cases and should be considered an emerging threat for TB control in Tehran. In addition, the extensive pre-existing drug resistance profiles of MDR/XDR strains will further challenge TB diagnostics in the region.

Keywords: Mycobacterium tuberculosis; Tehran; extensive drug resistance; multidrug resistance; whole-genome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology
  • Cross-Sectional Studies
  • Drug Resistance, Multiple, Bacterial / genetics
  • Genes, Bacterial / genetics
  • Genetic Variation*
  • Genome, Bacterial / genetics*
  • Genotype
  • Humans
  • Iran / epidemiology
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / classification
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics*
  • Phylogeny
  • Retrospective Studies
  • Tuberculosis, Multidrug-Resistant / epidemiology
  • Tuberculosis, Multidrug-Resistant / microbiology*
  • Tuberculosis, Multidrug-Resistant / transmission
  • Tuberculosis, Pulmonary / epidemiology
  • Tuberculosis, Pulmonary / microbiology*
  • Tuberculosis, Pulmonary / transmission

Substances

  • Antitubercular Agents