Thursday, March 02, 20172:00 PM - 3:00 PMCNLS Conference Room (TA-3, Bldg 1690)|
Membrane perturbing properties of toxin mycolactone from Mycobacterium ulcerans
Cesar Lopez BautistaT-6/CNLS
Mycolactone is the exotoxin produced by Mycobacterium ulcerans that is the key virulence factor behind the neglected tropical disease Buruli ulcer. Experiments have linked this toxin to a broad spectrum of biological effects within the host organism, including at least two molecular targets and the inhibition of protein uptake into the endoplasmic reticulum. We used coarse-grained molecular dynamics simulations, to study the interaction of mycolactone with pure and mixed lipid membranes. Using established techniques, we calculated the toxin’s preferential localization, membrane translocation, and impact on membrane physical and dynamical properties, lowering the transition temperature, compressibility modulus, and critical line tension at which pores can be stabilized. It also shows a tendency to behave as a linactant, a molecule that localizes at the boundary between different fluid lipid domains in membranes and promotes inter-mixing of domains. The implications of this property in the context of its cellular access, T-cell immunosuppression and therapeutic potential are discussed.
Host: Chris Neale