Search for new anti-bacterial drugs that inhibit bacterial chaperonins

Dr. Abdesalam Azem (PI) - TRDC


As key players in mediating protein folding in vivo, chaperonins are essential proteins for all prokaryotic and eukaryotic organisms.  In this proposal, we suggest identifying drugs that are able to specifically inhibit the function of bacterial chaperonins, thereby causing bacterial death but not host death.  We hope that such chemicals will constitute the basis for a future generation of antibiotics.  We present evidence that the bacterial and human chaperonins are much more distinct, structurally and functionally, than previously assumed.  Thus, it should be feasible to identify chemicals that inhibit the bacterial but not the human chaperonins.  We suggest a number of novel approaches (in vitro and in vivo functional assays) for the selection of  such specific compounds.  In addition to the use of chaperonin functional assays, the study will involve the use of structural biology and bioinformatics as well.  The ramifications of this work are great and include the development of new antibiotics against pathogenic bacteria, development of drugs that inhibit mitochondrial function (apoptosis) with implications for chemotherapy and finally, will contribute to a greater understanding of chaperonin function.