Dynamics of interaction between MA and cholesterol in tuberculosis

Abstract

Tuberculosis (TB) is a disease caused by the infection of Mycobacterium tuberculosis, which is progressively becoming multi-drug resistant (MDR). Understanding the mechanism by which the organism interacts with host lipids, infect macrophages and how components redistribute within the host could open the investigation of new ways of inhibiting and eradicating the infection suffered by patients world wide. Flow fluorometry of liposomes containing mycolic acids, which are â-hydroxy fatty acids with a long á-alkyl side chain of mycobacteria, may be useful to determine the dynamics of interaction of these lipids with the host membrane lipids and with cholesterol. This will increase the understanding about the structure-function relationship of mycolic acids in M.tb. It was shown in this thesis that natural mycolic acids had a unique property, it could exchange rapidly between liposomes in the presence and absence of cholesterol even at low temperatures. Rapid exchange of mycolic acids within the host could be the mechanism by which trafficking of mycobacterial lipids comes about, ultimately leading to immune response modulation beyond the infected cell. It also provides direction for future investigation to bring about new serodiagnostic tests based on lipid antigens. Although flow fluorometry as a modern technique was unable to resolve the exchange of mycolic acids in relation with other lipids, a unique property of mycolic acids was demonstrated for the first time, that of rapid exchange. Copyright