Molecular characterisation of multidrug-resistant Mycobacterium tuberculosis isolates from a high-burden tuberculosis state in Brazil

Epidemiol Infect. 2019 Jan:147:e216. doi: 10.1017/S0950268819001006.

Abstract

Tuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131 Mycobacterium tuberculosis (M.tb) DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of the katG, inhA and rpoB genes and RDRio sublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRio deletion was observed in 42 (32%) of the M.tb isolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%) M.tb isolates, we found mutations associated with rifampicin (RIF) resistance in rpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance in katG and inhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in the rpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.

Keywords: Brazil; drug resistance; genotyping; tuberculosis (TB).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Antitubercular Agents / therapeutic use
  • Bacterial Proteins / genetics*
  • Brazil / epidemiology
  • Cost of Illness
  • DNA-Directed RNA Polymerases / genetics
  • Databases, Factual
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Female
  • Genotype
  • Humans
  • Incidence
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Minisatellite Repeats / genetics
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / isolation & purification
  • Retrospective Studies
  • Risk Assessment
  • Sex Distribution
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / epidemiology*
  • Tuberculosis, Multidrug-Resistant / genetics*
  • Young Adult

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • DNA-Directed RNA Polymerases