Erucic acid attenuates post-influenza secondary Staphylococcus aureus infection by modulating VCAM-1 and CEACAM-1 expression and gut dysbiosis.

Erucic acid demonstrated protective efficacy against post-influenza secondary S. aureus infection in mice, reducing lung index, weight loss, and lung damage.

• The mouse model involved sequential infection with influenza PR8 virus followed by S. aureus.
• Erucic acid treatment reduced lung index compared to untreated infected controls.
• Weight loss was attenuated in erucic acid-treated mice relative to the secondary infection group.
• Histological analysis confirmed relief of lung damage in treated animals.

Erucic acid significantly inhibited PR8 infection-mediated increases in S. aureus adhesion both in vitro and in vivo.

• PR8 (influenza A) infection promoted S. aureus adhesion to host cells and lung tissue.
• Erucic acid treatment reduced this enhanced bacterial adhesion in cell-based assays.
• In vivo experiments confirmed reduced S. aureus adhesion in lung tissue of erucic acid-treated mice.
• The anti-adhesive effect was demonstrated using BEAS-2B human bronchial epithelial cells in vitro.

VCAM-1 and CEACAM-1 were identified as key adhesion molecules mediating erucic acid's anti-adhesive effects.

• RNA-seq analysis was used to identify candidate adhesion molecules.
• Molecular docking and molecular dynamics simulations supported erucic acid's interaction with VCAM-1 and CEACAM-1.
• Immunohistochemistry, qPCR, and Western blot (WB) validated erucic acid's regulatory effect on both VCAM-1 and CEACAM-1 expression.
• Erucic acid suppressed PR8-mediated upregulation of both VCAM-1 and CEACAM-1.

Both VCAM-1 and CEACAM-1 overexpression in mouse lungs promoted S. aureus adhesion, but only VCAM-1 overexpression enhanced bacterial adhesion in vitro in BEAS-2B cells.

• Overexpression experiments were conducted both in vivo (mouse lungs) and in vitro (BEAS-2B cells).
• In mouse lungs, overexpression of either VCAM-1 or CEACAM-1 increased S. aureus adhesion.
• Paradoxically, in BEAS-2B cells, only VCAM-1 overexpression enhanced bacterial adhesion.
• CEACAM-1 overexpression did not enhance S. aureus adhesion to BEAS-2B cells in vitro.
• Erucic acid treatment markedly attenuated the VCAM-1 overexpression-mediated enhancement of bacterial adhesion in vitro.

Erucic acid administration alleviated gut dysbiosis induced by post-influenza secondary S. aureus infection.

• 16S rRNA sequencing was used to characterize gut microbiome composition.
• Post-influenza secondary S. aureus infection caused gut dysbiosis in mice.
• Erucic acid treatment markedly attenuated this gut dysbiosis.
• The gut microbiome modulation represents an additional mechanism by which erucic acid may confer protection against secondary bacterial infection.