Proteomics of host-bacterial interactions: new insights from dual perspectives

Mass-spectrometry (MS)-based proteomics is a powerful and robust platform for studying the interactions between biological systems during health and disease. Bacterial infections represent a significant threat to global health and drive the pursuit of novel therapeutic strategies to combat emerging and resistant pathogens. During infection, the interplay between a host and pathogen determines the ability of the microbe to survive in a hostile environment and promotes an immune response by the host as a protective measure. It is the protein-level changes from either biological system that define the outcome of infection, and MS-based proteomics provides a rapid and effective platform to identify such changes. In particular, proteomics detects alterations in protein abundance, quantifies protein secretion and (or) release, measures an array of post-translational modifications that influence signaling cascades, and profiles protein-protein interactions through protein complex and (or) network formation. Such information provides new insight into the role of known and novel bacterial effectors, as well as the outcome of host cell activation. In this Review, we highlight the diverse applications of MS-based proteomics in profiling the relationship between bacterial pathogens and the host. Our work identifies a plethora of strategies for exploring mechanisms of infection from dual perspectives (i.e., host and pathogen), and we suggest opportunities to extrapolate the current knowledgebase to other biological systems for applications in therapeutic discovery.