Interbacterial Chemical Communication‐Triggered Nascent Proteomics

Abstract

Metabolic labeling with clickable noncanonical amino acids has enabled nascent proteome profiling, which can be performed in a cell-type-specific manner. However, nascent proteomics in an intercellular communication-dependent manner remains challenging. Here we develop communication-activated profiling of protein expression (CAPPEX), which integrates the LuxI/ LuxR quorum sensing circuit with the cell-type-specific nascent proteomics method to enable selective clicklabeling of newly synthesized proteins in a specific bacterium upon receiving chemical signals from another reporter bacterium. CAPPEX reveals that E. coli competes with Salmonella for tryptophan as the precursor for indole, and the resulting indole suppressed the expression of virulence factors in Salmonella. This tryptophan-indole axis confers attenuation of Salmonella invasion in host cells and living mice. The CAPPEX strategy should be widely applicable for investigating various interbacterial communication processes.

Nascent Proteomics: Chemical Tools for Monitoring Newly Synthesized Proteins

“…Furthermore, a bisected version of NLL‐MetRS has been developed to enable cell‐selective NSP labeling with ANL under the control of an AND gate of two promoters [79] . More recently, the Chen group integrated a quorum sensing genetic circuit to trigger the expression of NLL‐MetRS to enable communication‐triggered nascent proteomic analysis in complex bacterial populations [80] . Applying this method termed communication‐activated profiling of protein expression (CAPPEX), a tryptophan‐indole axis was discovered to contribute to the colonization resistance of Salmonella by commensal E. coli .…”