Genetic Polymorphism in Mycobacterium tuberculosis Isolates from Patients with Chronic Multidrug-Resistant Tuberculosis

• Published in: The Journal of infectious diseases 2004-07, Vol.190 (1), p.99-106
• Main Authors: Post, Frank A., Willcox, Paul A., Mathema, Barun, Steyn, Lafras M., Shean, Karen, Ramaswamy, Srinivas V., Graviss, Edward A., Shashkina, Elena, Kreiswirth, Barry N., Kaplan, Gilla
• Format: Article
• Language: English
• Subjects: Adult; Antitubercular Agents - pharmacology; Antitubercular Agents - therapeutic use; Antituberculars; Bacteria; Bacterial diseases; Bacterial Proteins - genetics; Biological and medical sciences; Chronic Disease; DNA Transposable Elements - genetics; Drug resistance; Drug Resistance, Multiple, Bacterial - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetic mutation; Genotypes; Human bacterial diseases; Human immunodeficiency virus; Humans; Infectious diseases; Male; Medical sciences; Microbial Sensitivity Tests; Microbiology; Middle Aged; Multidrug resistant tuberculosis; Mutation; Mycobacterium tuberculosis; Mycobacterium tuberculosis - classification; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - isolation & purification; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Public health; Pulmonary tuberculosis; Sequence Analysis, DNA; Sputum; Sputum - microbiology; Tuberculosis; Tuberculosis and atypical mycobacterial infections; Tuberculosis, Multidrug-Resistant - drug therapy; Tuberculosis, Multidrug-Resistant - microbiology
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/421501

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 MDRTB, 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 sputumderived 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.