Multi-omics driven biomarker discovery and pathological insights into Pseudomonas aeruginosa pneumonia.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a leading cause of hospital-acquired pneumonia, contributing significantly to morbidity and mortality, especially in immunocompromised patients. Understanding the molecular mechanisms underlying this infection is crucial for developing targeted therapeutic strategies. This study aims to elucidate the local and systemic pathways and biomarkers involved in the pathogenesis of P. aeruginosa pneumonia through an integrated multi-omics approach. METHODS: We performed a comprehensive proteomic and metabolomic analysis on clinical samples from patients diagnosed with P. aeruginosa pneumonia, including both bronchoalveolar lavage fluid (BALF) and serum to capture local and systemic host responses. Data were analyzed using advanced statistical techniques to identify differentially expressed proteins and metabolites. Pathway enrichment analysis was performed to highlight significant biological processes associated with the infection. RESULTS: Our findings revealed a significant upregulation of biomarkers associated with neutrophil extracellular traps (NETs) and oxidative stress, underscoring their pivotal roles in immune response and inflammatory pathology. Key proteins such as LCN2, CALR, and TPI1 were identified as central players in NET formation and oxidative stress pathways. Our integrated approach uniquely highlights the simultaneous local and systemic impact of NETs and oxidative stress. Additionally, by analyzing both BALF and serum, we observed distinct disruptions in metabolic pathways, particularly those related to amino acid metabolism and energy production, suggesting a bioenergetic crisis in response to infection. The combined analysis revealed key interactions between local and systemic immune responses, indicating a reprogramming of host energy pathways to meet the heightened immune demands, contributing to disease progression. CONCLUSION: This study provides a comprehensive understanding of the molecular mechanisms driving P. aeruginosa pneumonia by uniquely integrating BALF and serum analyses to explore both local and systemic host responses. Our findings highlight the dual role of NETs in both pathogen containment and tissue damage, as well as the metabolic reprogramming required to sustain immune activity. The identification of key biomarkers and disrupted pathways presents promising targets for therapeutic intervention, with the potential to refine diagnostic precision and improve patient outcomes. CLINICAL TRIAL NUMBER: Not applicable.