Cell surface ß-lactamase recruitment: A facile selection to identify protein-protein interactions.

Protein-protein interactions (PPIs) are central to many cellular processes, and the identification of novel PPIs is a critical step in the discovery of protein therapeutics. Simple methods to identify naturally existing or laboratory evolved PPIs are therefore valuable research tools. We have developed a facile selection that links PPI-dependent ß-lactamase recruitment on the surface of Escherichia coli with resistance to ampicillin. Bacteria displaying a protein that forms a complex with a specific protein-ß-lactamase fusion are protected from ampicillin-dependent cell death. In contrast, bacteria that do not recruit ß-lactamase to the cell surface are killed by ampicillin. Given its simplicity and tunability, we anticipate this selection will be a valuable addition to the palette of methods for illuminating and interrogating PPIs.

Antibody-Recruitment as a Therapeutic Strategy: A Brief History and Recent Advances.

Antibodies are a significant and growing sector within the global pharmaceutical industry. The popularity of antibodies as therapeutics derives from - at least in part - evolvable affinity for virtually any disease-relevant cell surface receptor, as well as unique immunotherapeutic mechanisms of action, including neutralization, antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC). While advances in the large-scale expression and purification of therapeutic antibodies have been made, these remain costly and laborious tasks. Agents that redirect endogenous antibodies to target a pathogen or malignant cell obviate the need for new antibody discovery and production. Chimeric antibody-recruiting technologies consist of a target cell surface receptor binding domain, and an endogenous antibody-binding domain. By design, these agents bring endogenous antibodies to the surface of a target pathogen or diseased cell, which can result in targeted cytotoxicity by antibody-dependent mechanisms. This review highlights seminal contributions and recent advances in this growing and important therapeutic field.