Cell surface β‐lactamase recruitment: A facile selection to identify protein–protein interactions

Abstract

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 β‐lactamase recruitment on the surface of Escherichia coli with resistance to ampicillin. Bacteria displaying a protein that forms a complex with a specific protein‐β‐lactamase fusion are protected from ampicillin‐dependent cell death. In contrast, bacteria that do not recruit β‐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.