Structural and functional studies of S-layers in pathogenic bacilli.

S-layers are proteinaceous 2D crystals that cover the cell surface of many Bacteria and near all Archaea. They require a high metabolic investment from the cell and are thought to serve as exoskeleton, protection against harmful environments, molecular sieve for nutrient uptake and a contact zone with host cells in case of pathogenic bacteria. B. anthracis, the etiological agent of anthrax, represents an interesting model to study S-layers. In its vegetative form, two mutually exclusive S-layers, Sap and EA1, sequentially appear at the cell surface in a growth phase-dependent manner. Our recent
findings exposed the disruption of S-layer integrity as a mechanism with therapeutic potential in S-layer carrying pathogens. Building on these novel findings, we will investigate the molecular and physiological basis for the energetically costly replacement of an S- layer in function of the cell cycle, host infection and stress responses. To do so, we will further explore the role of B. anthracis S-layers as virulence factors mediating adhesion to host tissues, and
characterize the receptor specificities and structural determinants involved in host recognition. Then we will focus on the determination of developmental, environmental and host triggers that induce such cell surface remodeling. These combined studies will provide fundamental insights into the biological function and purpose of S- layers in Bacilli, with a particular emphasis on pathogenic species