Multi-omic signatures of host response associated with presence, type, and outcome of enterococcal bacteremia

Despite the prevalence and severity of enterococcal bacteremia (EcB), the mechanisms underlying systemic host responses to the disease remain unclear. Here, we present an extensive study that profiles molecular differences in plasma from EcB patients using an unbiased multi-omics approach. We performed shotgun proteomics and metabolomics on 105 plasma samples, including those from EcB patients and healthy volunteers. Comparison between healthy volunteer and EcB-infected patient samples revealed significant disparities in proteins and metabolites involved in the acute phase response, inflammatory processes, and cholestasis. Several features distinguish these two groups with remarkable accuracy. Cross-referencing EcB signatures with those of Staphylococcus aureus bacteremia revealed shared reductions in cholesterol metabolism proteins and differing responses in platelet alpha granule and neutrophil-associated proteins. Characterization of Enterococcus isolates derived from patients facilitated a nuanced comparison between EcB caused by Enterococcus faecalis and Enterococcus faecium, uncovering reduced immunoglobulin abundances in E. faecium cases and features capable of distinguishing the underlying microbe. Leveraging extensive patient metadata, we now have identified features associated with mortality or survival, revealing significant multi-omic differences and pinpointing histidine-rich glycoprotein and fetuin-B as features capable of distinguishing survival status with excellent accuracy. Altogether, this study aims to culminate in the creation of objective risk stratification algorithms—a pivotal step toward enhancing patient management and care. To facilitate the exploration of this rich data source, we provide a user-friendly interface at https://gonzalezlab.shinyapps.io/EcB_multiomics/ . IMPORTANCE Enterococcus infections have emerged as the second most common nosocomial infection, with enterococcal bacteremia (EcB) contributing to thousands of patient deaths annually. To address a lack of ...