AutoriLaventie BJ1, Potrich C, Atmanène C, Saleh M, Joubert O, Viero G, Bachmeyer C, Antonini V, Mancini I, Cianferani-Sanglier S, Keller D, Colin DA, Bourcier T, Anderluh G, van Dorsselaer A, Dalla Serra M, Prévost G
AbstractPVL (Panton-Valentine leukocidin) and other Staphylococcus aureus ?-stranded pore-forming toxins are important virulence factors involved in various pathologies that are often necrotizing. The present study characterized leukotoxin inhibition by selected SCns (p-sulfonato-calix[n]arenes): SC4, SC6 and SC8. These chemicals have no toxic effects on human erythrocytes or neutrophils, and some are able to inhibit both the activity of and the cell lysis by leukotoxins in a dose-dependent manner. Depending on the type of leukotoxins and SCns, flow cytometry revealed IC50 values of 6-22 ?M for Ca2+ activation and of 2-50 ?M for cell lysis. SCns were observed to affect membrane binding of class S proteins responsible for cell specificity. Electrospray MS and surface plasmon resonance established supramolecular interactions (1:1 stoichiometry) between SCns and class S proteins in solution, but not class F proteins. The membrane-binding affinity of S proteins was Kd=0.07-6.2 nM. The binding ability was completely abolished by SCns at different concentrations according to the number of benzenes (30-300 ?M; SC8>SC6>>SC4). The inhibitory properties of SCns were also observed in vivo in a rabbit model of PVL-induced endophthalmitis. These calixarenes may represent new therapeutic avenues aimed at minimizing inflammatory reactions and necrosis due to certain virulence factors.
RivistaBiochemical Journal
Impact factor
Pagina inizio559
Pagina fine571
Autori IBFMauro DALLA SERRA, Valeria ANTONINI, Gabriella VIERO, Cristina POTRICH
Linee di Ricerca IBFMD.P01.028.001