[Photorhabdus virulence cassette promotes bacterial invasion into macrophages by activating NF-κB and MAPK signaling...

Area of Science:

• Microbiology
• Immunology
• Molecular Biology

Background:

• Photorhabdus bacteria, including Photorhabdus asymbiotica (Pa), are Gram-negative pathogens causing insect and human infections.
• The mechanisms underlying Pa's transkingdom pathogenicity remain largely unknown.
• The Photorhabdus virulence cassette (PVC) is a key genetic element in Pa and other pathogens.

Purpose of the Study:

• To investigate the role of the Photorhabdus virulence cassette (PVC) in Pa's interaction with mammalian cells.
• To elucidate the signaling pathways involved in PVC-mediated pathogenicity.
• To understand how PVC influences bacterial invasion of host cells.

Main Methods:

• RNA-sequencing (RNA-seq) and quantitative PCR (qPCR) to analyze host gene expression.
• Western blotting to confirm pathway activation.
• Inhibitor studies targeting NF-κB and MAPK pathways.
• p65 translocation assays to assess NF-κB activation.
• Phagocytosis assays with cytoskeleton inhibitors.

Main Results:

• PVC treatment significantly activated NF-κB and MAPK signaling pathways in mammalian macrophages.
• Western blotting and p65 translocation assays confirmed NF-κB and MAPK activation.
• PVC promoted bacterial phagocytosis by macrophages in the early stages of infection.
• Cytoskeleton inhibitors partially blocked PVC-induced phagocytosis.

Conclusions:

• The Photorhabdus virulence cassette (PVC) plays a crucial role in Pa pathogenicity by activating NF-κB and MAPK signaling pathways.
• PVC-mediated signaling enhances bacterial invasion through macrophage phagocytosis.
• This study provides novel insights into the molecular mechanisms of Pa's transkingdom infection.