Cytokine-expression patterns reveal coordinated immunological programs associated with persistent MRSA bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a common, life-threatening infection that imposes up to 30% mortality even when appropriate therapy is used. Despite in vitro efficacy, antibiotics often fail to resolve the infection in vivo, resulting in persistent MRSA bacteremia. Recently, several genetic, epigenetic, and proteomic correlates of persistent outcomes have been identified. However, the extent to which single variables or composite patterns operate as independent predictors of outcome or reflect shared underlying mechanisms of persistence is unknown. To explore this question, we employed a tensor-based integration of host transcriptional and proteomic data across a well-characterized cohort of patients with persistent and resolving MRSA bacteremia outcomes. Tensor-based data integration yielded high correlative accuracy with persistence and revealed immunologic signatures shared across both the transcriptomic and proteomic datasets. We find that elevated proliferation of mature granulocytes associates with resolving bacteremia outcomes. In contrast, patients with persistent bacteremia heterogeneously exhibit correlates of granulocyte dysfunction or immature granulocyte proliferation. Collectively, these results suggest that transcriptional and proteomic correlates of persistent versus resolving bacteremia outcomes are complex and may not be disclosed by conventional modeling. However, a tensor-based integration approach can help to reveal consensus molecular mechanisms in an interpretable manner.