Current Molecular Medicine - Volume 7, Issue 3, 2007

It is some twenty years since the first genes were cloned from pathogenic mycobacteria and 8 years since the complete DNA sequence of a Mycobacterium tuberculosis genome was published. When the first genes were cloned TB was commonly regarded as a beaten disease; we had fully effective chemotherapy, an adequate vaccine (BCG) and the remaining problem (people dying elsewhere) was to be solved by field Read More

A framework was developed to provide an integrated view of mycobacterial growth and its regulation. The topics reviewed include the properties of cell cultures and their relation to properties of individual cells, cell sizes and macromolecular compositions, uptake of nutrients through the cell envelope, protein biosynthesis, core metabolic pathways, generation of an electrochemical gradient of protons, ATP synthesis and the c Read More

The replication and growth of Mycobacterium tuberculosis are fundamentally linked to the synthesis and extension of its complex cell wall. Incorporation of new wall material must be tightly regulated so that its deposition does not compromise the extant structure. M. tuberculosis also produces an impressive array of complex bioactive lipids that are intimately involved in pathogenesis and protective immunity. The profil Read More

Mycobacterium tuberculosis encounters a range of stimuli in the host. Understanding the environmental cues that initiate the transcriptional response of M. tuberculosis, which enable the bacterium to replicate and/or survive in the host, will provide markers that are specific to different stages of disease, further refining the search for improved treatments and vaccines. Studying M. tuberculosis gene expression in vivo is Read More

Analysis of the changing mRNA expression profile of Mycobacterium tuberculosis though the course of infection promises to advance our understanding of how mycobacteria are able to survive the host immune response. The difficulties of sample extraction from distinct mycobacterial populations, and of measuring mRNA expression profiles of multiple genes has limited the impact of gene expression studies on our inte Read More

There is an urgent need for new drugs to treat tuberculosis. During the last forty years the only drugs to have been developed are variations on existing ones, but new drug candidates must offer improvements over existing agents. In particular, we require new drugs having novel mechanisms of action that are active against drug-resistant strains and also kill persistent bacilli, thus shortening the length of chemoth Read More

During the past two decades, a number of variable genetic sequences have been uncovered that permit molecular typing of Mycobacterium tuberculosis complex (MTC) organisms. Since the determination of the M. tuberculosis, and later M. bovis, genome sequences, the nature of these variable genetic sequences has become more evident, permitting a clearer recognition of which molecular tools lend themselves best to Read More

Due to the failure of chemotherapy and the only available vaccine, BCG, to control tuberculosis (TB) disease, there is an urgent need to develop new vaccines and therapeutics. The identification of correlates of immune protection or “biomarkers” will facilitate the rational design of vaccines and drugs for the prevention and clearance of TB infection. Although it is known that IFN-γ is essential for protective immunity, animal a Read More

We need to understand what is different about susceptibility to tuberculosis (TB) in developing countries where most TB occurs, and where the current vaccine, Bacillus Calmette et Guerin (BCG) usually fails to protect. The presence of a background mixed IFN-γ and Th2 response to mycobacterial antigens before infection with M. tuberculosis (Mtb), and the development of a large IL-4 response during progressive TB, Read More