title: Genetic polymorphism in Mycobacterium tuberculosis isolates from patients with chronic multidrug-resistant tuberculosis.
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.
authors.affiliation: Infectious Diseases Unit, University of Cape Town, Cape Town, South Africa.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Post
authors.forename: Paul A
authors.initials: PA
authors.lastname: Willcox
authors.forename: Barun
authors.initials: B
authors.lastname: Mathema
authors.forename: Lafras M
authors.initials: LM
authors.lastname: Steyn
authors.forename: Karen
authors.initials: K
authors.lastname: Shean
authors.forename: Srinivas V
authors.initials: SV
authors.lastname: Ramaswamy
authors.forename: Edward A
authors.initials: EA
authors.lastname: Graviss
authors.forename: Elena
authors.initials: E
authors.lastname: Shashkina
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics; D002908:Chronic Disease; D004251:DNA Transposable Elements / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004251:DNA Transposable Elements