Characterization of the interaction of daptomycin with bacterial liposomal analogues

Efforts to curb the prevalence of antibiotic resistant bacteria are unable to keep up with the aggressive adaptation of these bacterial species to existing antibiotics. Therefore, examining the interaction of existing antibiotics with bacteria may reveal previously unknown bacterial susceptibilities. Daptomycin is a typical second-line treatment for antibiotic-resistant gram positive bacterial strains, like methicillin-resistant Staphylococcus aureus (MRSA). Its proposed mechanism of action is to bind to the negatively charged phosphatidyglycerol (PG) head groups of the bacterial cytoplasmic membrane via a calcium ion dependent process. However, the specific mechanisms by which daptomycin exerts its bacteriocidality are currently unknown. It has been hypothesized that bacterial membrane rigidity may have an effect on susceptibility to daptomycin. Additionally, there is evidence to suggest that the charge of the bacterial membrane charge affects daptomycin's mechanism of action. Our study aims to systematically analyze the interaction of daptomycin with liposomal bacterial analogues by varying the rigidity and the zeta potential of the liposomes. Our results show possible mechanisms for targeting daptomycin resistance in gram positive bacteria.M.S.Includes bibliographical referencesby Nevin Varghes