Monitoring host-pathogen interactions using chemical proteomics

With the rapid emergence and the dissemination of microbial resistance to conventional chemotherapy, the shortage of novel antimicrobial drugs has raised a global health threat. As molecular interactions between microbial pathogens and their mammalian hosts are crucial to establish virulence, pathogenicity, and infectivity, a detailed understanding of these interactions has the potential to reveal novel therapeutic targets and treatment strategies. Bidirectional molecular communication between microbes and eukaryotes is essential for both pathogenic and commensal organisms to colonise their host. In particular, several devastating pathogens exploit host signalling to adjust the expression of energetically costly virulent behaviours. Chemical proteomics has emerged as a powerful tool to interrogate the protein interaction partners of small molecules and has been successfully applied to advance host-pathogen communication studies. Here, we present recent significant progress made by this approach and provide a perspective for future studies. We review how chemical proteomic tools have been used to elucidate biological processes at the interface of bacteria and eukaryotic hosts, which can be important in the establishment of pathogenicity.