Molecular interactions between bacterial and host cells can profoundly impact human health and disease. We study enzymes and other proteins whose biochemical activity dynamically shapes these interactions in the context of gastrointestinal infections. We use a diverse set of chemical and biological tools to address fundamental questions regarding biochemical crosstalk at the host-microbe interface: What enzymes are active during an infection? How does pathogen-associated stress (e.g., from the immune system or antimicrobials) influence protein function in infected cells? What molecular processes do these proteins regulate? By interrogating the functional proteome of bacterial infections, we aim to uncover biochemical pathways that will advance our understanding of gastrointestinal diseases like stomach cancer and cholera and generate new leads for therapeutic targets, activity-based diagnostics, and drug delivery systems.