E-MTAB-4093 - The effect of growth rate on pyrazinamide activity in Mycobacterium tuberculosis; insights for early bactericidal activity
Last updated on 2 December 2015, released on 25 March 2016
Mycobacterium tuberculosis H37Rv
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.
transcription profiling by array, growth condition design
The effect of growth rate on pyrazinamide activity in Mycobacterium tuberculosis - insights for early bactericidal activity?. Pullan ST, Allnutt JC, Devine R, Hatch KA, Jeeves RE, Hendon-Dunn CL, Marsh PD, Bacon J. :205 (2016), PMID:27184366
The effect of growth rate on pyrazinamide activity in Mycobacterium tuberculosis; insights for early bactericidal activity. Steven T. Pullan, Jon C. Allnutt, Rebecca Devine, Kim A Hatch, Rose E. Jeeves, Charlotte L. Hendon-Dunn, Philip D. Marsh, Joanna Bacon.