Visualizing Staphylococcus aureus pathogenic membrane modification within the host infection environment by
William J Perry1, Caroline M Grunenwald2, Raf Van de Plas3
1Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37212, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University, Nashville, TN 37232, USA.
This study visualizes Staphylococcus aureus virulence factors in host tissues using advanced imaging. It reveals specific lipid distributions linked to immune evasion and varied bacterial responses to host defenses.
Area of Science:
- Microbiology
- Immunology
- Biophysics
Background:
- Bacterial pathogens utilize virulence factors for host colonization and dissemination.
- Visualizing bacterial virulence factor regulation within host tissues remains a significant challenge.
- Multimodal imaging offers a powerful approach to study host-pathogen molecular interactions.
Purpose of the Study:
- To visualize Staphylococcus aureus (S. aureus) envelope modifications within infected host tissues.
- To integrate high spatial resolution imaging mass spectrometry with microscopy for enhanced visualization.
- To investigate the spatial distribution and role of specific lipids in S. aureus pathogenicity.
Main Methods:
- Utilized multimodal imaging by integrating fluorescence microscopy with matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance imaging mass spectrometry (MALDI-FTICR-IMS).
- Employed fluorescent bacterial reporters to track S. aureus within infected murine and human tissues.
- Applied data-driven image fusion to correlate bacterial localization with molecular lipid profiles.
Main Results:
- Successfully visualized S. aureus envelope modifications, specifically lysyl-phosphatidylglycerol (LPG) lipids, within infected tissues.
- Identified LPG lipids localized to distinct bacterial communities, suggesting a targeted response.
- Observed differential distribution of LPGs in murine versus human infections, indicating host-specific microbial adaptations.
- Linked the absence of LPGs to decreased pathogenicity, highlighting their role in immune system evasion.
Conclusions:
- Multimodal imaging is effective for visualizing bacterial virulence factor localization and host-pathogen interactions in situ.
- S. aureus exhibits heterogeneous, spatially organized virulence factor expression in response to host defenses.
- Lysyl-phosphatidylglycerols are crucial for S. aureus survival against innate immunity and show varied distribution patterns in different hosts.
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