Hancock Pilot Project Summary

Carbon source availability in a host environment drives the establishment of colonization and infection by microbial pathogens. A major contributor to cellular physiology in bacteria is the control of metabolism by carbon catabolite repression. In Gram-positive bacteria, this is governed by a protein complex of CcpA and phosphorylated Hpr [Ser-46-P]. We have observed that a deletion of ccpA in E. faecalis increases expression of catabolic pathways necessary for the utilization of host-derived glycans, particularly N-linked glycoproteins.
We have recently observed that glycosyl hydrolases are abundantly expressed under glucose deplete environments which is commonly observed in host conditions. In addition to liberating glycans from host proteins, adapted pathogens are able to sense, import and process the glycans into a form that maximizes energy potential. We have identified a glycan importer as well as glycan sensor that is able to control the synthesis of the importer to regulate the efficient uptake of the released glycans. Using chemically synthesized glycans, we will explore what glycans drive sensing and activation of the glycan importer, as well as any accessory gene products required to utilize host glycans to increase the metabolic fitness of E. faecalis in the host environment.