Intracellular proteins moonlighting as bacterial adhesion factors

Pathogenic and commensal, or probiotic, bacteria employ adhesins on the cell surface to attach to and interact with the host. Dozens of the adhesins that play key roles in binding to host cells or extracellular matrix were originally identified as intracellular chaperones or enzymes in glycolysis or other central metabolic pathways. Proteins that have two very different functions, often in two different subcellular locations, are referred to as moonlighting proteins. The intracellular/surface moonlighting proteins do not contain signal sequences for secretion or known sequence motifs for binding to the cell surface, so in most cases is not known how these proteins are secreted or how they become attached to the cell surface. A secretion system in which a large portion of the pool of each protein remains inside the cell while some of the pool of the protein is partitioned to the cell surface has not been identified. This may involve a novel version of a known secretion system or it may involve a novel secretion system. Understanding the processes by which intracellular/cell surface moonlighting proteins are targeted to the cell surface could provide novel protein targets for the development of small molecules that block secretion and/or association with the cell surface and could serve as lead compounds for the development of novel antibacterial therapeutics.