Staphylococcus aureus β-toxin exerts anti-angiogenic effects by inhibiting re-endothelialization and neovessel formation
Staphylococcus aureus is the causative agent of numerous severe human infections associated with significant morbidity and mortality worldwide. S. aureus often targets the vascular endothelium to interfere with proper host responses during invasive infections. In this study, we provide evidence that S. aureus {beta}-toxin inhibits wound repair mechanisms in human endothelial cells by preventing cell proliferation and migration. These findings were confirmed in a rabbit aortic explant model where {beta}-toxin impedes sprout formation. Decreased cell proliferation was accompanied by decreased production of the angiogenic proteins endothelin-1, IGFBP-3, thrombospondin-1, TIMP-1, and TIMP-4. Meanwhile, inhibited wound repair was marked by increased HGF secretion from endothelial cells, likely a marker of endothelial cell damage. Together, these findings establish a mechanistic role for {beta}-toxin where it inhibits proper tissue repair processes that likely promote S. aureus infective niche.