Background: The commensal nasal microbiota Staphylococcus epidermidis (S. epidermidis) can suppress influenza A virus (IAV) activity in the host lung by modulating the microcellular environment. However, the metabolic mechanisms underlying this antiviral effect remain unclear. This study employs a novel combination of atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) and Orbitrap secondary ion mass spectrometry (OrbiSIMS) imaging to investigate the metabolic interactions between nasal microbiota and IAV infection in mouse lung tissue.
Results: By utilizing this high-resolution dual-platform MS imaging (MSI) approach, we achieved high spatial resolution mapping of metabolic alterations, revealing polyamine metabolism as a key pathway mediating the antiviral effects of S. epidermidis. Our findings demonstrate that S. epidermidis inoculation downregulates polyamine metabolism, significantly suppressing IAV replication, a mechanism confirmed through targeted polyamine supplementation. Additionally, sulfate/sulfite metabolism was identified as a crucial metabolic pathway modulated in IAV-infected and S. epidermidis-treated lungs.
Significance: This study represents the first application of integrated AP-MALDI and OrbiSIMS MSI to antiviral metabolomic analysis, providing critical insights into host-microbiota interactions in respiratory infections. Our results provide a foundation for utilizing spatial metabolomics to explore novel therapeutic targets for viral infections and highlight the potential of nasal microbiota in respiratory defense. These findings could advance MS-based biomarker discovery and antiviral drug development.
Keywords: Influenza A virus; MALDI-MSI; Nasal microbiota; OrbiSIMS; Staphylococcus epidermidis.
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