Abstract
In this study, using the Hain GenoType MTBDRsl assays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations in gyrA in Mycobacterium tuberculosis 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.
| Original language | English |
|---|---|
| Article number | e02169-16 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 61 |
| Issue number | 4 |
| ISSN | 0066-4804 |
| DOIs | |
| Publication status | Published - 04.2017 |
Funding
We thank Armand Van Deun for his advice regarding this study and Priti Rathod for organizational support. T.M.W. is a University of Oxford National Institute for Health Research (NIHR) academic clinical lecturer. N.A. was supported by a doctoral study fund from Colciencias. T.S. was supported by grants from the Swedish Heart and Lung Foundation and the Marianne and Marcus Wallenberg Foundation. F.C. was supported by the Wellcome Trust (grant 201344/Z/16/Z). D.W.C. and T.E.A.P. are NIHR senior investigators supported by the NIHR Oxford Biomedical Research Centre, NIHR Oxford Health Protection Research Unit on Healthcare Associated Infection and Antimicrobial Resistance (grant HPRU-2012-10041), and the Health Innovation Challenge Fund (grant T5-358). S.N. was supported by grants from the German Center for Infection Research (DZIF), the European Union TB-PAN-NET (grant FP7-223681), and PathoNgenTrace (grant 278864). S.J.P. was supported by the Health Innovation Challenge Fund (grants HICF-T5-342 and WT098600), a parallel funding partnership between the UK Department of Health and Wellcome Trust. C.U.K. is a junior research fellow at Wolfson College, Cambridge. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health, Public Health England, or the Wellcome Trust. T.S. is a member of the EUCAST subgroup on antimycobacterial susceptibility testing. J.P., S.J.P., and C.U.K. have collaborated with Illumina, Inc., on a number of scientific projects. J.P. has received funding for travel and accommodation from Pacific Biosciences, Inc., and Illumina, Inc. S.N. is a consultant for the Foundation for Innovative New Diagnostics. S.J.P. has received funding for travel and accommodation from Illumina, Inc. C.U.K. was a technical advisor for the Tuberculosis Guideline Development Group of the World Health Organization (WHO) during the meeting that endorsed the Hain MTBDRsl assay but resigned from that position; T.S. was an observer at that meeting. C.U.K. is a consultant for the Foundation for Innovative New Diagnostics, which includes work on behalf of the WHO. The Bill and Melinda Gates Foundation, Janssen Pharmaceutical, and PerkinElmer covered C.U.K.'s travel and accommodation to present at meetings. The European Society of Mycobacteriology awarded C.U.K. the Gertrud Meissner Award, which is sponsored by Hain Lifescience.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
