Some synonymous and nonsynonymous gyrA mutations in Mycobacterium tuberculosis lead to systematic false-positive fluoroquinolone resistance results with the Hain GenoType MTBDRsl assays

Adebisi Ajileye; Nataly Alvarez; Matthias Merker; Timothy M. Walker; Suriya Akter; Kerstin Brown; Danesh Moradigaravand; Thomas Schoen; Soenke Andres; Viola Schleusener; Shaheed V. Omar; Francesc Coll; Hairong Huang; Roland Diel; Nazir Ismail; Julian Parkhill; Bouke C. de Jong; Tim E. A. Peto; Derrick W. Crook; Stefan Niemann; Jaime Robledo; E. Grace Smith; Sharon J. Peacock; Claudio U. Koeser

doi:10.1128/AAC.02169-16

Some synonymous and nonsynonymous gyrA mutations in Mycobacterium tuberculosis lead to systematic false-positive fluoroquinolone resistance results with the Hain GenoType MTBDRsl assays

Adebisi Ajileye, Nataly Alvarez, Matthias Merker, Timothy M. Walker, Suriya Akter, Kerstin Brown, Danesh Moradigaravand, Thomas Schoen, Soenke Andres, Viola Schleusener, Shaheed V. Omar, Francesc Coll, Hairong Huang, Roland Diel, Nazir Ismail, Julian Parkhill, Bouke C. de Jong, Tim E. A. Peto, Derrick W. Crook, Stefan NiemannJaime Robledo, E. Grace Smith, Sharon J. Peacock, Claudio U. Koeser

Mycobacteriology

Research output: Contribution to journal › A1: Web of Science-article › peer-review

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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	UNSP e02169-16
Journal	Antimicrobial Agents and Chemotherapy
Volume	61
Issue number	4
Number of pages	8
ISSN	0066-4804
DOIs	https://doi.org/10.1128/AAC.02169-16
Publication status	Published - 2017

Keywords

Mycobacterium tuberculosis
Hain GenoType MTBDRsl
fluoroquinolones
LINE PROBE ASSAY
DRUG-RESISTANCE
ANTIBIOTIC-RESISTANCE
XDR TUBERCULOSIS
CLINICAL-SAMPLES
COMPLEX STRAINS
VERSION V2.0
PERFORMANCE
SUSCEPTIBILITY
2ND-LINE

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10.1128/AAC.02169-16

2017aache02169

Cite this

Ajileye, A., Alvarez, N., Merker, M., Walker, T. M., Akter, S., Brown, K., Moradigaravand, D., Schoen, T., Andres, S., Schleusener, V., Omar, S. V., Coll, F., Huang, H., Diel, R., Ismail, N., Parkhill, J., de Jong, B. C., Peto, T. E. A., Crook, D. W., ... Koeser, C. U. (2017). Some synonymous and nonsynonymous gyrA mutations in Mycobacterium tuberculosis lead to systematic false-positive fluoroquinolone resistance results with the Hain GenoType MTBDRsl assays. Antimicrobial Agents and Chemotherapy, 61(4), [UNSP e02169-16]. https://doi.org/10.1128/AAC.02169-16

Ajileye, Adebisi ; Alvarez, Nataly ; Merker, Matthias ; Walker, Timothy M. ; Akter, Suriya ; Brown, Kerstin ; Moradigaravand, Danesh ; Schoen, Thomas ; Andres, Soenke ; 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. ; Koeser, Claudio U. / Some synonymous and nonsynonymous gyrA mutations in Mycobacterium tuberculosis lead to systematic false-positive fluoroquinolone resistance results with the Hain GenoType MTBDRsl assays. In: Antimicrobial Agents and Chemotherapy. 2017 ; Vol. 61, No. 4.

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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.",

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Ajileye, A, Alvarez, N, Merker, M, Walker, TM, Akter, S, Brown, K, Moradigaravand, D, Schoen, T, Andres, S, Schleusener, V, Omar, SV, Coll, F, Huang, H, Diel, R, Ismail, N, Parkhill, J, de Jong, BC, Peto, TEA, Crook, DW, Niemann, S, Robledo, J, Smith, EG, Peacock, SJ & Koeser, CU 2017, 'Some synonymous and nonsynonymous gyrA mutations in Mycobacterium tuberculosis lead to systematic false-positive fluoroquinolone resistance results with the Hain GenoType MTBDRsl assays', Antimicrobial Agents and Chemotherapy, vol. 61, no. 4, UNSP e02169-16. https://doi.org/10.1128/AAC.02169-16

Some synonymous and nonsynonymous gyrA mutations in Mycobacterium tuberculosis lead to systematic false-positive fluoroquinolone resistance results with the Hain GenoType MTBDRsl assays. / Ajileye, Adebisi; Alvarez, Nataly; Merker, Matthias; Walker, Timothy M.; Akter, Suriya; Brown, Kerstin; Moradigaravand, Danesh; Schoen, Thomas; Andres, Soenke; 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.; Koeser, Claudio U.

In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 4, UNSP e02169-16, 2017.

Research output: Contribution to journal › A1: Web of Science-article › peer-review

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T1 - Some synonymous and nonsynonymous gyrA mutations in Mycobacterium tuberculosis lead to systematic false-positive fluoroquinolone resistance results with the Hain GenoType MTBDRsl assays

AU - Ajileye, Adebisi

AU - Alvarez, Nataly

AU - Merker, Matthias

AU - Walker, Timothy M.

AU - Akter, Suriya

AU - Brown, Kerstin

AU - Moradigaravand, Danesh

AU - Schoen, Thomas

AU - Andres, Soenke

AU - Schleusener, Viola

AU - Omar, Shaheed V.

AU - Coll, Francesc

AU - Huang, Hairong

AU - Diel, Roland

AU - Ismail, Nazir

AU - Parkhill, Julian

AU - de Jong, Bouke C.

AU - Peto, Tim E. A.

AU - Crook, Derrick W.

AU - Niemann, Stefan

AU - Robledo, Jaime

AU - Smith, E. Grace

AU - Peacock, Sharon J.

AU - Koeser, Claudio U.

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N2 - 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.

AB - 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.

KW - Mycobacterium tuberculosis

KW - Hain GenoType MTBDRsl

KW - fluoroquinolones

KW - LINE PROBE ASSAY

KW - DRUG-RESISTANCE

KW - ANTIBIOTIC-RESISTANCE

KW - XDR TUBERCULOSIS

KW - CLINICAL-SAMPLES

KW - COMPLEX STRAINS

KW - VERSION V2.0

KW - PERFORMANCE

KW - SUSCEPTIBILITY

KW - 2ND-LINE

U2 - 10.1128/AAC.02169-16

DO - 10.1128/AAC.02169-16

M3 - A1: Web of Science-article

VL - 61

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

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ER -