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

Author:

Ajileye Adebisi1,Alvarez Nataly23,Merker Matthias45,Walker Timothy M.6,Akter Suriya7,Brown Kerstin1,Moradigaravand Danesh8,Schön Thomas910,Andres Sönke11,Schleusener Viola4,Omar Shaheed V.12,Coll Francesc13,Huang Hairong14,Diel Roland15,Ismail Nazir12,Parkhill Julian8ORCID,de Jong Bouke C.7,Peto Tim E. A.6,Crook Derrick W.616,Niemann Stefan45,Robledo Jaime23,Smith E. Grace1,Peacock Sharon J.81317,Köser Claudio U.17ORCID

Affiliation:

1. Public Health England West Midlands Public Health Laboratory, Heartlands Hospital, Birmingham, United Kingdom

2. Bacteriology and Mycobacteria Unit, Corporación Para Investigaciones Biológicas, Medellín, Colombia

3. Universidad Pontificia Bolivariana, Medellín, Colombia

4. Division of Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany

5. German Center for Infection Research (DZIF), Partnersite Hamburg-Lübeck-Borstel, Borstel, Germany

6. Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom

7. Mycobacteriology Unit, Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium

8. Wellcome Trust Sanger Institute, Hinxton, United Kingdom

9. Department of Clinical and Experimental Medicine, Division of Medical Microbiology, Linköping University, Linköping, Sweden

10. Department of Clinical Microbiology and Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden

11. Division of Mycobacteriology, National Tuberculosis Reference Laboratory, Research Center Borstel, Borstel, Germany

12. Centre for Tuberculosis, National Institute for Communicable Diseases, Johannesburg, South Africa

13. London School of Hygiene & Tropical Medicine, London, United Kingdom

14. National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China

15. Institute of Epidemiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

16. Public Health England, Microbiology Services, London, United Kingdom

17. Department of Medicine, University of Cambridge, Cambridge, United Kingdom

Abstract

ABSTRACT In this study, using the Hain GenoType MTBDR sl 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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference49 articles.

1. Diagnostic Performance of the New Version (v2.0) of GenoType MTBDRslAssay for Detection of Resistance to Fluoroquinolones and Second-Line Injectable Drugs: a Multicenter Study

2. WHO recommendations on shorter treatment of multidrug-resistant tuberculosis

3. World Health Organization. 2016. The use of molecular line probe assays for the detection of resistance to second-line anti-tuberculosis drugs. Policy guidance. http://www.who.int/tb/areas-of-work/laboratory/WHOPolicyStatementSLLPA.pdf?ua=1. Accessed 31 July 2016.

4. World Health Organization. 2016. Online annexes (5–8) to WHO policy guidance: the use of molecular line probe assay for the detection of resistance to second-line anti-tuberculosis drugs. http://www.who.int/tb/areas-of-work/laboratory/OnlineAnnexes_MTBDRsl.pdf?ua=1. Accessed 2 August 2016.

5. World Health Organization. 2016. WHO treatment guidelines for drug-resistant tuberculosis, 2016 update. World Health Organization, Geneva, Switzerland. https://www.ncbi.nlm.nih.gov/books/NBK390455/. Accessed 3 March 2016.

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