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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Effect of mutation and genetic background on drug resistance in Mycobacterium tuberculosis
Antimicrobial Agents and Chemotherapy, Volume 56, No. 6, Year 2012
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Description
Bacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistant Mycobacterium tuberculosis isolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of firstline drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains, katG mutations were associated with high-level and inhA promoter mutations with low-level drug resistance. Only katG(S315T) (65.6% of all isoniazid-resistant strains) and inhA promoter -15C/T (22.7%) were found in molecular clusters. M. tuberculosis lineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6; P<0.0001). Lineage 1 was associated with inhA promoter -15C/T mutations (OR, 6.4; 95% CI, 2.0 to 20.7; P=0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages; P<0.0001). In conclusion, M. tuberculosis drug resistance mutations were associated with various levels of drug resistance and transmission, and M. tuberculosis lineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds in M. tuberculosis drug resistance. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3370767/bin/supp_56_6_3047__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3370767/bin/supp_56.6.3047_SuppMaterial_REV.pdf
Authors & Co-Authors
Fenner, Lukas
Switzerland, Bern
University of Bern
Egger, Matthias
Switzerland, Bern
University of Bern
Bödmer, Thomas
Switzerland, Bern
University of Bern
Altpeter, Ekkehardt Siegfried
Switzerland, Bern
Federal Office of Public Health Foph
Zwahlen, Marcel
Switzerland, Bern
University of Bern
Jaton, Katia
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Pfyffer, Gaby E.
Unknown Affiliation
Borrell, Sònia
Switzerland, Allschwil
Swiss Tropical and Public Health Institute Swiss Tph
Switzerland, Basel
Universitat Basel
Furrer, Hansjakob
Switzerland, Bern
University of Bern
Calmy, Alexandra L.
Switzerland, Geneva
Hôpitaux Universitaires de Genève
Fehr, Jan Sven
Switzerland, Zurich
Universität Zürich
Stalder, Jesica Mazza
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Böttger, Erik Christian
Switzerland, Zurich
Universität Zürich
Gagneux, Sébastien P.
Switzerland, Allschwil
Swiss Tropical and Public Health Institute Swiss Tph
Switzerland, Basel
Universitat Basel
Statistics
Citations: 96
Authors: 14
Affiliations: 7
Identifiers
Doi:
10.1128/AAC.06460-11
ISSN:
10986596
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Case-Control Study
Study Approach
Quantitative