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bioRxiv · 10.1101/2023.12.13.571096

Staphylococcus aureus can use an alternative pathway to be internalized by osteoblasts in absence of β1 integrins

Mouton, W.·Tricou, L.-P.·Cara, A.·Trouillet-Assant, S.·Bouvard, D.·Laurent, F.·Diot, A.·Josse, J.
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Abstract

Staphylococcus aureus main internalization mechanism in osteoblasts relies on a tripartite interaction between bacterial fibronectin-binding proteins, extracellular matrix soluble fibronectin, and osteoblasts {beta}1 integrins. Caveolins, and particularly caveolin-1, have shown to limit the plasma membrane microdomain mobility, and consequently reduce the uptake of S. aureus in keratinocytes. In this study, we aimed to deepen our understanding of the molecular mechanisms underlying S. aureus internalization in osteoblasts. Mechanistically, S. aureus internalization requires endosomal recycling {beta}1 integrins as well as downstream effectors such as Src, Rac1, and PAK1. Surprisingly, in {beta}1 integrin deficient osteoblasts, S. aureus internalization is restored when Caveolin-1 is absent and requires v{beta}3/v{beta}5 integrins as backup fibronectin receptors. Altogether, our data support that {beta}1 integrins regulate the level of detergent-resistant membrane at the plasma membrane in a an endosomal and Caveolin-1 dependent manner. SUMMARY STATEMENTStaphylococcus aureus can be internalized by osteoblasts via a different mechanism than the main 5{beta}1/fibronectin/fibronectin-binding protein that likely involves v{beta}3 or v{beta}5 integrin.

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Mouton, W., Tricou, L.-P., Cara, A., Trouillet-Assant, S., Bouvard, D., Laurent, F., Diot, A., Josse, J.. 2023-12-13. Staphylococcus aureus can use an alternative pathway to be internalized by osteoblasts in absence of β1 integrins. https://doi.org/10.1101/2023.12.13.571096

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