Vitamin C preventsS. aureusinfections of endothelial cells through its interaction with specific residues in the active site of gC1qR/p33 involved in direct entry, notably SER230, ASN345, ILE348, TYR224, ASN346, SER347, and GLU438, and its potential inhibitory effects on FnBPs, α5β1, and Protein A molecules

Abstract

Staphylococcus aureus (S. aureus), often perceived as an extracellular pathogenic agent, exhibits a remarkable ability to penetrate host cells, including endothelial, epithelial, and osteoblastic cells, significantly contributing to the pathogenesis of infections. A significant pathway for this invasion appears to involve the bacterium's binding to the α5β1 integrin via a fibronectin bridge, followed by phagocytosis. Additionally, S. aureus presents staphylococcal protein A, a cell wall protein that binds to the Fc and Fab regions of immunoglobulins, playing a crucial role in virulence and immune evasion, and can also bind directly to the gC1qR receptor on endothelial cells. Furthermore, vitamin C is recognized for its antimicrobial and immunomodulatory properties, offering potential for reducing the risk of infection. Considering the aforementioned elements, our study focused on exploring the potential effects of vitamin C on the interactions between S. aureus and endothelial cells. Thus, we particularly examined two aspects: on the one hand, interactions involving fibronectin-binding proteins (FnBPs) proteins and human α5β1 integrin, and on the other hand, the interaction between vitamin C and the direct entry receptor (the globular heads of complement component 1q receptor [gC1qR/p33], also known as hyaluronic acid binding protein 1 [HABP1]). To achieve this, we utilized molecular modeling assays, primarily relying on molecular docking.