Transcriptomics

Dataset Information

42

The effect of growth rate on pyrazinamide activity in Mycobacterium tuberculosis; insights for early bactericidal activity


ABSTRACT: Background: Pyrazinamide (PZA) plays an essential part in the shortened 6-month tuberculosis (TB) treatment course due to its activity against slow-growing, semi-dormant organisms. We tested the paradigm that PZA preferentially targets slow growing cells of Mycobacterium tuberculosis that remain after the initial kill by isoniazid, by observing the response of either slow growing or fast growing bacilli to differing concentrations of PZA. Methods: M. tuberculosis H37Rv was grown in continuous culture at either a constant fast growth rate (Mean Generation Time [MGT] of 23.1 h) or slow growth rate (69.3 h MGT) at a controlled dissolved oxygen tension of 10% and a controlled acidity at pH 6.3 ± 0.1. The cultures were exposed to step-wise increases in the concentration of PZA (25 µg ml-1 to 250 µg ml-1) every 2 MGTs, and bacterial survival was measured. PZA-induced global gene expression was explored for each increase in PZA-concentration, using microarray.

ORGANISM(S): Mycobacterium tuberculosis H37Rv  

SUBMITTER: Rose Elizabeth E Jeeves  Steve T Pullan  Joanna Bacon       

PROVIDER: E-MTAB-4093 | ArrayExpress| 2015-12-02

REPOSITORIES: ArrayExpress

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Publications

The effect of growth rate on pyrazinamide activity in Mycobacterium tuberculosis - insights for early bactericidal activity?

Pullan Steven T ST   Allnutt Jon C JC   Devine Rebecca R   Hatch Kim A KA   Jeeves Rose E RE   Hendon-Dunn Charlotte L CL   Marsh Philip D PD   Bacon Joanna J  

BMC infectious diseases 20160517


Pyrazinamide (PZA) plays an essential part in the shortened six-month tuberculosis (TB) treatment course due to its activity against slow-growing and non-replicating organisms. We tested whether PZA preferentially targets slow growing cells of Mycobacterium tuberculosis that could be representative of bacteria that remain after the initial kill with isoniazid (INH), by observing the response of either slow growing or fast growing bacilli to differing concentrations of PZA.M. tuberculosis H37Rv w  ...[more]

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