title: Some Synonymous and NonsynonymousgyrAMutations in Mycobacterium tuberculosis Lead to Systematic False-Positive Fluoroquinolone Resistance Results with the Hain GenoType MTBDRslAssays.
abstract: In this study, using the Hain GenoType MTBDRslassays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations ingyrAinMycobacterium tuberculosisresult 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.
authors.affiliation: Public Health England West Midlands Public Health Laboratory, Heartlands Hospital, Birmingham, United Kingdom.
authors.forename: Adebisi
authors.initials: A
authors.lastname: Ajileye
authors.affiliation: Bacteriology and Mycobacteria Unit, Corporación Para Investigaciones Biológicas, Medellín, Colombia.|Universidad Pontificia Bolivariana, Medellín, Colombia.
authors.forename: Nataly
authors.initials: N
authors.lastname: Alvarez
authors.affiliation: Division of Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany.|German Center for Infection Research (DZIF), Partnersite Hamburg-Lübeck-Borstel, Borstel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Merker
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Walker
authors.affiliation: Mycobacteriology Unit, Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Suriya
authors.initials: S
authors.lastname: Akter
authors.affiliation: Public Health England West Midlands Public Health Laboratory, Heartlands Hospital, Birmingham, United Kingdom.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Brown
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Danesh
authors.initials: D
authors.lastname: Moradigaravand
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Medical Microbiology, Linköping University, Linköping, Sweden.|Department of Clinical Microbiology and Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schön
authors.affiliation: Division of Mycobacteriology, National Tuberculosis Reference Laboratory, Research Center Borstel, Borstel, Germany.
authors.forename: Sönke
authors.initials: S
authors.lastname: Andres
authors.affiliation: Division of Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany.
authors.forename: Viola
authors.initials: V
authors.lastname: Schleusener
authors.affiliation: Centre for Tuberculosis, National Institute for Communicable Diseases, Johannesburg, South Africa.
authors.forename: Shaheed V
authors.initials: SV
authors.lastname: Omar
authors.affiliation: London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Francesc
authors.initials: F
authors.lastname: Coll
authors.affiliation: 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.
authors.forename: Hairong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Institute of Epidemiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Diel
authors.affiliation: Centre for Tuberculosis, National Institute for Communicable Diseases, Johannesburg, South Africa.
authors.forename: Nazir
authors.initials: N
authors.lastname: Ismail
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Julian
authors.identifier: 0000-0002-7069-5958
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Mycobacteriology Unit, Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Bouke C
authors.initials: BC
authors.lastname: de Jong
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Tim E A
authors.initials: TE
authors.lastname: Peto
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.|Public Health England, Microbiology Services, London, United Kingdom.
authors.forename: Derrick W
authors.initials: DW
authors.lastname: Crook
authors.affiliation: Division of Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany.|German Center for Infection Research (DZIF), Partnersite Hamburg-Lübeck-Borstel, Borstel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Niemann
authors.affiliation: Bacteriology and Mycobacteria Unit, Corporación Para Investigaciones Biológicas, Medellín, Colombia.|Universidad Pontificia Bolivariana, Medellín, Colombia.
authors.forename: Jaime
authors.initials: J
authors.lastname: Robledo
authors.affiliation: Public Health England West Midlands Public Health Laboratory, Heartlands Hospital, Birmingham, United Kingdom.
authors.forename: E Grace
authors.initials: EG
authors.lastname: Smith
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, United Kingdom.|London School of Hygiene & Tropical Medicine, London, United Kingdom.|Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.affiliation: Department of Medicine, University of Cambridge, Cambridge, United Kingdom cuk21@cam.ac.uk.
authors.forename: Claudio U
authors.identifier: 0000-0002-0232-846X
authors.initials: CU
authors.lastname: Köser
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001681:Biological Assay; D027081:DNA Gyrase / Q000235:genetics* / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005189:False Positive Reactions; D024841:Fluoroquinolones / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D015345:Oligonucleotide Probes / Q000737:chemistry / Q000378:metabolism; D010802:Phylogeny; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D015345:Oligonucleotide Probes; D027081:DNA Gyrase
keywords: Hain GenoType MTBDRsl; Mycobacterium tuberculosis; fluoroquinolones