Structural and morphological changes in bacteria-membrane mimetic DPPE/DPPG/water systems induced by sulfadiazine

The effects of sulfadiazine (SD), one of the generally used antibiotics was studied on bacteria-membrane mimetic model systems consisting of pure dipalmitoylphosphatidylethanolamine (DPPE) and DPPE/dipalmitoylphosphatidylglycerol (DPPG) at 95/5, 80/20 and 50/50 DPPE/DPPG ratios by using differential scanning calorimetry (DSC), simultaneous small- and wide-angle X-ray scattering (SWAXS) and freeze-fracture technique. In the presence of SD, varied between 10-3 and 1 SD/lipid molar ratios, the 95/5 DPPE/DPPG system shows tendentious destruction in the layer arrangement which is accompanied by minor perturbations in the thermotropic behaviour. Moreover, at this lipid composition the addition of SD results in the formation of stacks of extremely extended flat bilayers. Systems having a higher DPPG molar ratio exhibit complex and diffuse morphologies. At 50/50 DPPE/DPPG ratio DPPG and SD act together and form large spherical vesicles. The uniform morphology is not accompanied by a regular lamellar arrangement. The range of the SD/lipid ratio, where the SD molecules are embedded into the lipid bilayers, extends to about 10-1. Over this limit the separation of SD molecules can be observed at all investigated DPPE/DPPG ratios.