A unique approach, combining defined and reproducible in vitro models with DNA
microarrays, has been developed to study environmental modulation of mycobacterial
gene expression. The gene expression profiles of samples of Mycobacterium tuberculosis,
from independent chemostat cultures grown under defined and reproducible
conditions, were found to be highly correlated. This approach is now being used to
study the effect of relevant stimuli, such as limited oxygen availability, on mycobacterial
gene expression. A modification of the chemostat culture system, enabling largevolume
controlled batch culture, has been developed to study starvation survival.
Cultures of M. tuberculosis have been maintained under nutrient-starved conditions
for extended periods, with 106 – 107 bacilli surviving in a culturable state after
100 days. The design of the culture system has made it possible to control the environment
and collect multiple time-course samples to study patterns of gene expression.
These studies demonstrate that it is possible to perform long-term studies and obtain
reproducible expression data using controlled and defined in vitro models