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