Abstract
ABSTRACTStaphylococcus aureusmain internalization mechanism in osteoblasts relies on a tripartite interaction between bacterial fibronectin-binding proteins, extracellular matrix soluble fibronectin, and osteoblasts’ β1 integrins. Caveolins, and particularly caveolin-1, have shown to limit the plasma membrane microdomain mobility, and consequently reduce the uptake ofS. aureusin keratinocytes. In this study, we aimed to deepen our understanding of the molecular mechanisms underlyingS. aureusinternalization in osteoblasts. Mechanistically,S. aureusinternalization requires endosomal recycling β1 integrins as well as downstream effectors such as Src, Rac1, and PAK1. Surprisingly, in β1 integrin deficient osteoblasts,S. aureusinternalization is restored when Caveolin-1 is absent and requires αvβ3/αvβ5 integrins as backup fibronectin receptors. Altogether, our data support that β1 integrins regulate the level of detergent-resistant membrane at the plasma membrane in a an endosomal and Caveolin-1 dependent manner.SUMMARY STATEMENTStaphylococcus aureuscan be internalized by osteoblasts via a different mechanism than the main α5β1/fibronectin/fibronectin-binding protein that likely involves αvβ3 or αvβ5 integrin.
Publisher
Cold Spring Harbor Laboratory