Investigating the role of bacterial sterol analogues in surface membrane properties and acclimation to environmental stress

• Applicant: Dr. James Saenz
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 527181518

The cell surface membrane is key to mediating interactions between cells and their environment. We previously demonstrated that bacterial sterol analogues known as hopanoids can be critical in determining the properties and function of bacterial surface membranes. Deletion of hopanoid synthesis not only alters surface membrane properties but also impairs membrane transport, rendering cells susceptible to antibiotics and toxins. Indeed, ours and other’s work has shown that hopanoids fortify bacteria against environmental stresses. However, it is not clear how the diverse hopanoid structures produced by bacteria contribute to cellular fitness and membrane properties over varying environmental growth conditions, and to what extent membrane properties can vary before crucial cellular functions like membrane transport fail. In this proposal we aim to elucidate the contribution of hopanoids to surface membrane biophysical properties and function. We will study two bacterial species that have surface membranes with distinct functions: the Gram-negative bacterial outer membrane of Methylobacterium extorquens, and the energy generating plasma membrane of Mesoplasma florum. By experimentally manipulating the hopanoid composition of surface membranes, we will characterize how three different hopanoid structural variants contribute to cellular adaptation to changing environmental conditions and contribute to membrane properties and function. To this end we propose to 1) define the effect of hopanoid pathway deletions on growth, 2) characterize how hopanoid structure influences surface membrane properties and 3) explore how hopanoid composition influences membrane efflux activity. Understanding the role of hopanoids in modulating membrane property and function will provide new tools for developing adaptive synthetic membranes, and will reveal lipidomic mechanisms for surface membrane adaptation to environmental change.

• DFG Programme: Research Grants