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

Secondary S. aureus infection following influenza is a critical complication with limited therapeutic options and leading to high mortality. This study investigates the potential application of erucic acid against post-influenza S. aureus infection. Our findings reveal that erucic acid demonstrated protective efficacy, as reduced lung index, weight loss, and relieved lung damage with post-influenza secondary S. aureus infection in mice. Erucic acid significantly inhibited the increase of S. aureus adhesion mediated by PR8 infection in vitro and in vivo. VCAM-1 and CEACAM-1 were identified as key adhesion molecules mediating erucic acid's anti-adhesive effects through RNA-seq, molecular docking, and molecular dynamics simulations. Immunohistochemistry, qPCR, and WB were performed to validate erucic acid's regulatory effect on VCAM-1 and CEACAM-1. Although both VCAM-1 and CEACAM-1 overexpression in mouse lungs promoted S. aureus adhesion, paradoxically, only VCAM-1 overexpression in vitro enhanced bacterial adhesion to BEAS-2B cells. Moreover, erucic acid treatment markedly attenuated this effect by suppressing VCAM-1 overexpression. 16S rRNA sequencing exhibited that erucic acid administration alleviates gut dysbiosis mediated by secondary S. aureus infection post-influenza. These findings reveal that erucic acid attenuated S. aureus adhesion by suppressing PR8-mediated upregulation of VCAM-1 and CEACAM-1. Furthermore, it mitigated pulmonary injury and gut dysbiosis induced by post-influenza secondary S. aureus infection. These findings are expected to offer novel therapeutic strategies for secondary S. aureus infection post-influenza.