Activity-Based Protein Profiling at the Host–Pathogen Interface

Abstract

Activity-based protein profiling (ABPP) is a technique for selectively detecting reactive amino acids in complex proteomes with the aid of chemical probes. Using probes that target catalytically active enzymes, ABPP can rapidly define the functional proteome of a biological system. In recent years, this approach has been increasingly applied to globally profile enzymes active at the host-pathogen interface of microbial infections. From in vitro co-culture systems to animal models of infection, these studies have revealed enzyme-mediated mechanisms of microbial pathogenicity, host immunity, and metabolic adaptation that dynamically shape pathogen interactions with the host.

Using click chemistry to study microbial ecology and evolution

“…In the earliest example, Speers and Cravatt labelled a sulfonate ester with an azide group and visualized serine hydrolase activities in cells using a copper-catalyzed click chemistry approach [ 60 ]. This approach was rapidly translated to the study of bacterial enzyme activities [ 61 ], such as bacterial glycosidases [ 62 ] and transferases, as well as the enzymes involved in host-pathogen interaction [ 63 ]. A recent example of this work that highlights a future direction is the combination of enzyme activity labelling with fluorescence in situ hybridization.…”

Activity‐based Tools for Interrogating Host Biology During Infection

“…In addition, studies comparing the probe‐based enrichment of enzymes in cells treated with or without a given drug (i. e., competitive ABPP) have enabled the identification and validation of putative drug targets [15–18] . Several recent review articles provide extensive coverage of these topics [19–22] . Here, we focus on the emerging role of ABPP as a tool for querying the host response to infection (Figure 2).…”

“…[15][16][17][18] Several recent review articles provide extensive coverage of these topics. [19][20][21][22] Here, we focus on the emerging role of ABPP as a tool for querying the host response to infection (Figure 2). We discuss how ABPP has been used to identify PTMs that regulate the signaling pathways of infected cells (Section 2), to profile functional changes in the host proteome during infection (Section 3), and to generate new leads for host-directed therapies (Section 4).…”

What you see is what you get: activity-based probes in single-cell analysis of enzymatic activities

“…The use of ABPP in a variety of different biological areas has been the subject of a number of reviews, e.g. for cancer (Nomura et al, 2010), plant biology (Morimoto and van der Hoorn, 2016), microbiology (Patel et al, 2019;Sharifzadeh et al, 2019;Whidbey and Wright, 2019), the host-pathogen interface (Kovalyova and Hatzios, 2019), host-virus interactions (Desrochers and Pezacki, 2019) or immunology (Borne et al, 2019;Koenders et al, 2019).…”