Project description:Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection.
Project description: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.
Project description:Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of tuberculosis (TB). we have used human monocyte and a mouse model of pulmonary TB to investigate whether treatment with PZA, in addition to its known anti-mycobacterial properties, modulate the host immune response during Mycobacterium tuberculosis (Mtb) infection. Mice were infected with Mtb and treatment with PZA was started at 28 days post-infection. At 42 days and 63 days post-infection, group of animals were euthanized and lung tissue was collected to isolate total RNA and used in microarray experiments. Mtb-infected, untreated animals served as controls.