Advances in activity-based diagnostics for infectious disease and microbiome health

In the human body, pathogens and the endogenous microbiome produce enzymes that aid in replication and survival. The activity from these enzymes as well as energy-dependent transport processes can be used as functional biomarkers for pathogen identification, antimicrobial treatment monitoring, and surveillance of microbiome health. To produce visual and/ or quantifiable readouts from this activity, concepts from chemical biology and nanomedicine have been used to develop signal-producing probes for patient samples or for direct administration in vivo. In the context of infection, activitybased diagnostics offer several potential advantages over current diagnostics including the ability to differentiate between active infection and sterile inflammation, which is made possible by targeting microbial enzymes with orthogonal activity to that of the host. In this review, we discuss new developments in the making of activity-based infection diagnostics and the beginnings of microbiome activity-based diagnostics.