A common mechanism of inhibition of the Mycobacterium tuberculosis mycolic acid biosynthetic pathway by isoxyl and thiacetazone.

Isoxyl (ISO) and thiacetazone (TAC), two prodrugs once used in the clinical treatment of tuberculosis, have long been thought to abolish Mycobacterium tuberculosis (M. tuberculosis) growth through the inhibition of mycolic acid biosynthesis, but their respective targets in this pathway have remained elusive. Here we show that treating M.

Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane.

New chemotherapeutics active against multidrug-resistant Mycobacterium tuberculosis are urgently needed. We report on the identification of an adamantyl urea compound that shows potent bactericidal activity against M. tuberculosis and a unique mode of action, namely the abolition of the translocation of mycolic acids from the cytoplasm, where they are synthesized to the periplasmic side of the plasma membrane and are in turn transferred onto cell wall arabinogalactan or used in the formation of virulence-associated, outer membrane, trehalose-containing glycolipids.

Interferon gamma responses to myelin peptides in multiple sclerosis correlate with a new clinical measure of disease progression.

The relationship between autoreactivity to myelin antigens and disease progression in multiple sclerosis (MS) is not fully understood. We addressed this relationship by cross-sectionally comparing an objective measure of MS disability with immune cytokine responses to myelin proteins. The ELISPOT assay was used to determine the ex vivo interferon gamma (IFNgamma) and interleukin-10 (IL-10) production by peripheral blood mononuclear cells (PBMCs) in response to peptides spanning the entire proteolipid protein (PLP) and myelin basic protein (MBP) molecules in 20 patients with relapsing-remitting (RR) MS and 27 age- and sex-matched healthy controls.