Project 1 - Inhibition of the oxireductase enzyme dpre1 of mycobacterium tuberculosis by two small compounds AND Project 2 - Investigating the role of the chaperonins of mycobacterium marinum

Inhibition of the oxidoreductase enzyme DprE1 of \(Mycobacterium\) \(tuberculosis\) by two small compounds DprE1 is an essential oxidoreductase enzyme found in the pathogen \(Mycobacterium\) \(tuberculosis\), the causative agent of the disease tuberculosis. The recent emergence of multi-drug (MDR-) and extensively-drug resistant (XDR-TB) strains of TB has highlighted the need for new drugs to complement an outdated treatment regimen. This project details the purification of DprE1 and the efforts made to characterize its interaction with two small compounds thought to be inhibitors, 1326 and 1328. The K\(_d\) value of each compound was determined and the design of two plasmids for the overexpression of \(Pseudomonas\) \(aeruginosa\) and \(Mycobacterium\) \(smegmatis\) DprE1 homologues was detailed. Investigating the role of the chaperonins of \(Mycobacterium\) \(marinum\) The chaperonins are a distinct subset of molecular chaperones. Homologues of the essential \(E.\) \(coli\) chaperonin GroEL have been identified across the \(Mycobacteria\) family of bacteria. Gene knockout of Cpn60.1 (\(cpn60\).1) has been achieved in \(Mycobacterium\) \(marinum\), a fish pathogen closely related to the human pathogen \(M.\) \(tuberculosis\). In this project efforts have been made to characterize this \(cpn60.1\)- knockout strain of \(M.\) \(marinum\); determining growth curves, lipid profiles, response to heat-shock, ability to form biofilms and relative levels of expression of each \(cpn\) gene under standard and heat shock growth conditions