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, Gerjo J, Dickinson, Laura ORCID: 0000-0001-5557-9396, Pertinez, Henry, Evangelopoulos, Dimitrios, McHugh, Timothy D, Bakker-Woudenberg, Irma AJM, Davies, Gerry R ORCID: 0000-0002-3819-490X and de Steenwinkel, Jurriaan EM
(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, 105. pp. 113-118.

Access the full-text of this item by clicking on the Open Access link.

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.

Item Type: Article
Uncontrolled Keywords: Lung, Animals, Mice, Inbred BALB C, Mycobacterium tuberculosis, Tuberculosis, Pulmonary, Disease Models, Animal, Ethambutol, Isoniazid, Pyrazinamide, Rifampin, Streptomycin, DNA, Bacterial, RNA, Ribosomal, 16S, Antitubercular Agents, Ribotyping, Colony Count, Microbial, Predictive Value of Tests, Nonlinear Dynamics, Time Factors, Female, Bacterial Load
Depositing User: Symplectic Admin
Date Deposited: 23 Jan 2019 14:43
Last Modified: 19 Jan 2023 01:06
DOI: 10.1016/j.tube.2017.05.002
Open Access URL: https://reader.elsevier.com/reader/sd/pii/S1472979...
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3031680