Immunity, microbial pathogenesis, and immunophilins: finding the keys, now where are the locks?
The discovery and clinical use of the immunosuppressants cyclosporin A, FK506, and rapamycin have greatly advanced solid organ and bone marrow transplantation. Though active as antibiotics against a variety of pathogens, their utility has been severely limited by toxicity. Research on the immunophilins, the major binding proteins of these drugs, has given new insights into protein folding and transport as well as mediators of signal transduction in mammalian cells. Microbial immunophilins may also have direct relevance to the intracellular survival of important human pathogens. Defining the mechanisms of enhanced virulence generated by these proteins holds great promise for understanding both the fundamental pathogenesis of these organisms and the immune response generated against them. Such an understanding may provide novel targets for the design of anti-infective agents as well as assist in the development of future immunosuppressives.
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Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.
Handschumacher
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D000591:Amino Acid Isomerases / Q000502:physiology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007239:Infections / Q000209:etiology*; D008213:Lymphocyte Activation / Q000187:drug effects; D019696:Peptidylprolyl Isomerase; D011090:Polyenes / Q000494:pharmacology; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins; D014774:Virulence
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D011090:Polyenes; D016572:Cyclosporine; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D020123:Sirolimus; D016559:Tacrolimus