Cooperative regulation in Acinetobacter baumannii Betaine-Choline-Carnitine transporters and the role of betaine in membrane vesicle trafficking during infection

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Our proposal focuses on the concerted molecular regulatory mechanism of the set of six BCCTs found in virulent A. baumannii strains. We postulate that together with mechanosensitive channels they are regulated by changes in the physical state of the membrane, e.g., by curvature, membrane tension or the lipid composition of the membrane, and that this lipid-regulation link them to virulence via specific lipid species. We will investigate the structure and function of these BCC membrane transporters and mechanosensitive channels and their cooperative regulation. Moreover, our aim is to decipher which lipid species regulate transcription and activity of the BCCTs and MS channels. In addition, we will investigate whether this group of membrane proteins can be linked to vesicle transport between inner and outer membrane. In summary, we would like to proof that betaine plays an important and complex role during host infection, which might be lead to new therapeutic approaches. Our group will employ the whole structural biology toolbox of X-ray crystallography, cryo-EM single particle analysis and cryo-EM tomography and single molecule FRET microscopy and HDX spectrometry.