Show simple item record

dc.contributor.authorLempens, P.
dc.contributor.authorMeehan, Conor J.
dc.contributor.authorVandelannoote, K.
dc.contributor.authorFissette, K.
dc.contributor.authorde Rijk, P.
dc.contributor.authorVan Deun, A.
dc.contributor.authorRigouts, L.
dc.contributor.authorde Jong, B.C.
dc.date.accessioned2019-09-16T21:34:12Z
dc.date.accessioned2019-10-02T11:49:30Z
dc.date.available2019-09-16T21:34:12Z
dc.date.available2019-10-02T11:49:30Z
dc.date.issued2018-02-19
dc.identifier.citationLempens P, Meehan CJ, Vandelannoote K et al (2018) Isoniazid resistance levels of Mycobacterium tuberculosis can largely be predicted by high-confidence resistance-conferring mutations. Scientific Reports. 8(1): article 3246.en_US
dc.identifier.urihttp://hdl.handle.net/10454/17278
dc.descriptionYesen_US
dc.description.abstractThe majority of Mycobacterium tuberculosis isolates resistant to isoniazid harbour a mutation in katG. Since these mutations cause a wide range of minimum inhibitory concentrations (MICs), largely below the serum level reached with higher dosing (15 mg/L upon 15–20 mg/kg), the drug might still remain partly active in presence of a katG mutation. We therefore investigated which genetic mutations predict the level of phenotypic isoniazid resistance in clinical M. tuberculosis isolates. To this end, the association between known and unknown isoniazid resistance-conferring mutations in whole genome sequences, and the isoniazid MICs of 176 isolates was examined. We found mostly moderate-level resistance characterized by a mode of 6.4 mg/L for the very common katG Ser315Thr mutation, and always very high MICs (≥19.2 mg/L) for the combination of katG Ser315Thr and inhA c-15t. Contrary to common belief, isolates harbouring inhA c-15t alone, partly also showed moderate-level resistance, particularly when combined with inhA Ser94Ala. No overt association between low-confidence or unknown mutations, except in katG, and isoniazid resistance (level) was found. Except for the rare katG deletion, line probe assay is thus not sufficiently accurate to predict the level of isoniazid resistance for a single mutation in katG or inhA.en_US
dc.description.sponsorshipEuropean Research Council (Starting Grant INTERRUPTB 311725 to CM, LR and BdJ), The Damien Foundationen_US
dc.language.isoenen_US
dc.rights(c) 2018 The Authors. This is an Open Access article distributed under the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/)en_US
dc.subjectAntimicrobial resistanceen_US
dc.subjectBacterial genomicsen_US
dc.subjectGenetic association studyen_US
dc.subjectInfectious-disease diagnosticsen_US
dc.subjectPathogensen_US
dc.titleIsoniazid resistance levels of Mycobacterium tuberculosis can largely be predicted by high-confidence resistance-conferring mutations.en_US
dc.status.refereedYesen_US
dc.date.Accepted2018-02-01
dc.typeArticleen_US
dc.type.versionPublished versionen_US
dc.identifier.doihttps://doi.org/10.1038/s41598-018-21378-x
dc.date.updated2019-09-16T20:34:14Z
refterms.dateFOA2019-10-02T11:49:58Z


Item file(s)

Thumbnail
Name:
Lempens_InhMic_SciRep_2018.pdf
Size:
2.186Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record