Genetic polymorphism in Mycobacterium tuberculosis isolates from patients with chronic multidrug-resistant tuberculosis

Frank A. Post, Paul A. Willcox, Barun Mathema, Lafras M. Steyn, Karen Shean, Srinivas V. Ramaswamy, Edward A. Graviss, Elena Shashkina, Barry N. Kreiswirth, Gilla Kaplan

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem because treatment is complicated, cure rates are well below those for drug-susceptible tuberculosis (TB), and patients may remain infectious for months or years, despite receiving the best available therapy. To gain a better understanding of MDR-TB, we characterized serial isolates recovered from 13 human immunodeficiency virus-negative patients with MDR-TB, by use of IS6110 restriction fragment-length polymorphism analysis, spacer oligonucleotide genotyping (i.e., "spoligotyping"), and sequencing of rpoB, katG, mabA-inhA (including promoter), pncA, embB, rpsL, rrs, and gyrA. For all 13 patients, chronic MDR-TB was caused by a single strain of Mycobacterium tuberculosis; 8 (62%) of the 13 strains identified as the cause of MDR-TB belonged to the W-Beijing family. The sputum-derived isolates of 4 (31%) of the 13 patients had acquired additional drug-resistance mutations during the study. In these 4 patients, heterogeneous populations of bacilli with different resistance mutations, as well as mixtures of drug-susceptible and drug-resistant genotypes, were observed. This genetic heterogeneity may require treatment targeted at both drug-resistant and drug-susceptible phenotypes.

Original languageEnglish (US)
Pages (from-to)99-106
Number of pages8
JournalJournal of Infectious Diseases
Volume190
Issue number1
DOIs
StatePublished - Jul 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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