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Assessment of treatment response by colony forming units, time to culture positivity and the molecular bacterial load assay compared in a mouse tuberculosis model

de Knegt, GJ; Dickinson, L; Pertinez, H; Evangelopoulos, D; McHugh, TD; Bakker-Woudenberg, IAJM; Davies, GR; (2017) Assessment of treatment response by colony forming units, time to culture positivity and the molecular bacterial load assay compared in a mouse tuberculosis model. Tuberculosis (Edinb) , 105 pp. 113-118. 10.1016/j.tube.2017.05.002. Green open access

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Abstract

The aim of the study is to compare counting of colony forming units (CFU), the time to positivity (TTP) assay and the molecular bacterial load (MBL) assay, and explore whether the last assays can detect a subpopulation which is unable to grown on solid media. CFU counting, TTP and the MBL assay were used to determine the mycobacterial load in matched lung samples of a murine tuberculosis model. Mice were treated for 24 weeks with 4 treatment arms: isoniazid (H) - rifampicin (R) - pyrazinamide (Z), HRZ-Streptomycin (S), HRZ - ethambutol (E) or ZES. Inverse relationships were observed when comparing TPP with CFU or MBL. Positive associations were observed when comparing CFU with MBL. Description of the net elimination of bacteria was performed for CFU vs. time, MBL vs. time and 1/TTP vs. time and fitted by nonlinear regression. CFU vs. time and 1/TTP vs. time showed bi-phasic declines with the exception of HRZE. A similar rank order, based on the alpha slope, was found comparing CFU vs. time and TTP vs. time, respectively HRZE, HRZ, HRZS and ZES. In contrast, MBL vs. time showed a mono-phasic decline with a flat gradient of elimination and a different rank order respectively, ZES, HRZ, HRZE and HRZS. The correlations found between methods reflects the ability of each to discern the general mycobacterial load. Based on the description of net elimination, we conclude that the MBL assay can detect a subpopulation of Mycobacterium tuberculosis which is not detected by the CFU or TTP assays.

Type: Article
Title: Assessment of treatment response by colony forming units, time to culture positivity and the molecular bacterial load assay compared in a mouse tuberculosis model
Location: Scotland
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.tube.2017.05.002
Publisher version: http://doi.org/10.1016/j.tube.2017.05.002
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Eastman Dental Institute > Microbial Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1557715
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