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Fibronectin-binding protein acts as Staphylococcus aureus invasin via fibronectin bridging to integrin alpha5beta1

Sinha, B.
Hartford, O. M.
Foster, T. J.
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Published in Cellular microbiology. 1999, vol. 1, no. 2, p. 101-117
Abstract The ability of Staphylococcus aureus to invade mammalian cells may explain its capacity to colonize mucosa and to persist in tissues after bacteraemia. To date, the underlying molecular mechanisms of cellular invasion by S. aureus are unknown, despite its high prevalence and difficulties in treatment. Here, we show cellular invasion as a novel function for an S. aureus adhesin, previously implicated solely in attachment. S. aureus, but not S. epidermidis, invaded epithelial 293 cells in a temperature- and F-actin-dependent manner. Formaldehyde-fixed and live bacteria were equally invasive, suggesting that no active bacterial process was involved. All clinical S. aureus isolates analysed, but only a subset of laboratory strains, were invasive. Fibronectin-binding proteins (FnBPs) acted as S. aureus invasins, because: (i) FnBP deletion mutants of invasive laboratory strains lost invasiveness; (ii) expression of FnBPs in noninvasive strains conferred invasiveness; and (iii) the soluble isolated fibronectin-binding domain of FnBP (D1-D4) completely blocked invasion. Integrin alpha5beta1 served as host cell receptor, which interacted with staphylococcal FnBPs through cellular or soluble fibronectin. FnBP-deficient mutants lost invasiveness for epithelial cells, endothelial cells and fibroblasts. Thus, fibronectin-dependent bridging between S. aureus FnBPs and host cell integrin alpha5beta1 is a conserved mechanism for S. aureus invasion of human cells. This may prove useful in developing new therapeutic and vaccine strategies for S. aureus infections.
Keywords Adhesins, BacterialAnti-Bacterial Agents/pharmacologyBacterial Proteins/ metabolismBlotting, WesternCarrier Proteins/ metabolismCell LineCell Membrane/ metabolism/ultrastructureCell SeparationCytochalasin D/pharmacologyFibronectins/ metabolismFlow CytometryFluorescein-5-isothiocyanate/metabolismFluorescent Dyes/metabolismHumansIntegrins/ metabolismKineticsLysostaphin/pharmacologyNucleic Acid Synthesis Inhibitors/pharmacologyPeptidesReceptors, VitronectinStaphylococcus aureus/drug effects/ metabolism/pathogenicity/ultrastructureTemperature
PMID: 11207545
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Research group Obésité et syndrome métabolique (803)
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SINHA, B. et al. Fibronectin-binding protein acts as Staphylococcus aureus invasin via fibronectin bridging to integrin alpha5beta1. In: Cellular microbiology, 1999, vol. 1, n° 2, p. 101-117. doi: 10.1046/j.1462-5822.1999.00011.x https://archive-ouverte.unige.ch/unige:7585

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Deposited on : 2010-06-21

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