Spatially-targeted proteomics of the host-pathogen interface during staphylococcal abscess formation

Abstract

Staphylococcus aureus is a common cause of invasive and life-threatening infections that are often multi-drug resistant. To develop novel treatment approaches, a detailed understanding of the complex host-pathogen interactions during infection is essential. This is particularly true for the molecular processes that govern the formation of tissue abscesses, as these heterogeneous structures are important contributors to staphylococcal pathogenicity. To fully characterize the developmental process leading to mature abscesses, temporal and spatial analytical approaches are required. Spatially targeted proteomic technologies, such as micro liquid extraction surface analysis, offer insight into complex biological systems including detection of bacterial proteins, and their abundance in the host environment. By analyzing the proteomic constituents of different abscess regions across the course of infection, we defined the immune response and bacterial contribution to abscess development through spatial and temporal proteomic assessment. The information gathered was mapped to biochemical pathways to characterize the metabolic processes and immune strategies employed by the host. These data provide insights into the physiological state of bacteria within abscesses and elucidate pathogenic processes at the host-pathogen interface.

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“…Our findings stem from the use of cutting-edge IMS technology that allows for untargeted discovery-based visualization of mo-lecular species, revealing spatial localization and intensity patterns that would be impossible to detect with traditional LC-MS/MS alone (Figure S1). This approach has been useful in a variety of host-pathogen interaction studies, such as in Staphylococcus aureus infections (Guiberson et al, 2021). The incorporation of MALDI IMS to study S. aureus soft tissue abscesses allows for molecular profiling of the bacterial nidus and surrounding tissue, revealing molecular changes that occur in this region during infection (Cassat et al, 2018).…”

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“…During infection, abscesses can form which offer a refuge for Staphylococcus to evade actions of immune response. In a recent study, microLESA was used to perform spatially targeted protein analysis of these abscesses, characterizing the proteomic composition of different regions of tissue throughout the course of an infection 139 . In doing so, the authors were able to evaluate bacterial contribution to the development of abscesses and characterize the metabolic processes during the course of an infection and study host immune response.…”