Increased Production of Outer Membrane Vesicles by Salmonella Interferes with Complement-Mediated Innate Immune...

Area of Science:

• Microbiology
• Immunology
• Bacterial Pathogenesis

Background:

• Bacterial outer membrane vesicles (OMVs) are crucial for host-pathogen interactions.
• The Salmonella PhoP-PhoQ (PhoPQ) system regulates outer membrane remodeling and OMV production.
• OMVs deliver virulence factors and influence pathogenesis.

Purpose of the Study:

• To investigate the role of PhoPQ-regulated OMVs in Salmonella survival against host immunity.
• To elucidate the mechanism by which OMVs interfere with complement activation.
• To quantify OMV size and number using nanoparticle tracking analysis.

Main Methods:

• Utilized nanoparticle tracking analysis to measure OMV size and concentration.
• Assessed the impact of PhoPQ-activated genes, specifically 'pagC', on OMV production.
• Investigated the interaction of OMVs and PagC with complement components (C3b, Factor H).

Main Results:

• PhoPQ-mediated OMV production significantly enhances bacterial survival by inhibiting complement activation.
• OMVs, particularly those enriched with PagC, protect Salmonella in a dose-dependent manner.
• PagC binds Factor H, leading to C3b inactivation and preventing complement-mediated lysis.
• Bacteria lacking OMVs were highly susceptible to complement-mediated killing.

Conclusions:

• PhoPQ-regulated OMV production, driven by PagC, is a key mechanism for Salmonella to evade innate immunity.
• PagC-enriched OMVs divert and inactivate complement components, protecting the bacteria.
• This evasion strategy supports Salmonella's survival during its extracellular phase and facilitates infection spread.