Jelena Antić-Stanković

The cmbT gene encodes a novel major facilitator multidrug resistance transporter in Lactococcus lactis.

Functional characterization of the multidrug resistance CmbT transporter was performed in Lactococcus lactis. The cmbT gene is predicted to encode an efflux protein homologous to the multidrug resistance major facilitator superfamily. The cmbT gene (1377 bp) was cloned and overexpressed in L. lactis NZ9000. Results from cell growth studies revealed that the CmbT protein has an effect on host cell resistance to lincomycin, cholate, sulbactam, ethidium bromide, Hoechst 33342, sulfadiazine, streptomycin, rifampicin, puromycin and sulfametoxazole. Moreover, in vivo transport assays showed that overexpressed CmbT-mediated extrusion of ethidium bromide and Hoechst 33342 was higher than in the control L. lactis NZ9000 strain. CmbT-mediated extrusion of Hoechst 33342 was inhibited by the ionophores nigericin and valinomycin known to dissipate proton motive force. This indicates that CmbT-mediated extrusion is based on a drug-proton antiport mechanism. Taking together results obtained in this study, it can be concluded that CmbT is a novel major facilitator multidrug resistance transporter candidate in L. lactis, with a possible signaling role in sulfur metabolism.

Synthesis, Cytotoxicity and Computational Study of Novel Protoberberine Derivatives

A novel and efficient synthetic route has been developed for the preparation of protoberberine derivatives. The methodology designed to control, primarily, substitution patterns on the terminal rings, was used to access a small array of these compounds. Initial biological profiling suggested anticancer potential of synthesised derivatives while structure-based target fishing has identified their potential targets and has established rational bases for further structural modifications. Although the activities need further improvement, our study demonstrated that the described approach may be useful in the discovery of the novel lead compounds.