Some Synonymous and Nonsynonymous gyrA Mutations in Mycobacterium tuberculosis Lead to Systematic False-Positive Fluoroquinolone Resistance Results with the Hain GenoType MTBDR sl Assays

• Published in: Antimicrobial agents and chemotherapy 2017-04, Vol.61 (4)
• Main Authors: Ajileye, Adebisi, Alvarez, Nataly, Merker, Matthias, Walker, Timothy M, Akter, Suriya, Brown, Kerstin, Moradigaravand, Danesh, Schön, Thomas, Andres, Sönke, Schleusener, Viola, Omar, Shaheed V, Coll, Francesc, Huang, Hairong, Diel, Roland, Ismail, Nazir, Parkhill, Julian, de Jong, Bouke C, Peto, Tim E A, Crook, Derrick W, Niemann, Stefan, Robledo, Jaime, Smith, E Grace, Peacock, Sharon J, Köser, Claudio U
• Format: Article
• Language: English
• Subjects: Antitubercular Agents - pharmacology; Biological Assay; DNA Gyrase - genetics; DNA Gyrase - metabolism; Drug Resistance, Multiple, Bacterial - genetics; False Positive Reactions; Fluoroquinolones - pharmacology; Gene Expression; Humans; Mutation; Mycobacterium tuberculosis - classification; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - isolation & purification; Oligonucleotide Probes - chemistry; Oligonucleotide Probes - metabolism; Phylogeny; Tuberculosis, Multidrug-Resistant - drug therapy; Tuberculosis, Multidrug-Resistant - microbiology
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.02169-16

In this study, using the Hain GenoType MTBDR assays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations in in result in systematic false-resistance results to fluoroquinolones by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings.