Document Detail

para-sulfonato-calix[n]arenes inhibit staphylococcal bicomponent leukotoxins by supramolecular interactions.
MedLine Citation:
PMID:  23282185     Owner:  NLM     Status:  Publisher    
Panton-Valentine leukocidin (PVL) and other S. aureus β-stranded pore-forming toxins are important virulence factors involved in various but often necrotizing pathologies. This study characterized leukotoxin inhibition by selected para-sulfonato-calix[n]arenes (SCn): SC4, SC6 and SC8. These chemicals have no toxic effects on human erythrocytes or neutrophils, and some are able to inhibit both activity and cell lysis by leukotoxins in a dose-dependent manner. Depending on leukotoxins and SCn, flow cytometry revealed IC50 values between 6-22 µM for Ca2+-activation and between 2-50 µM for cell lysis. SCn were observed to affect membrane binding of class S proteins responsible for cell specificity. Electrospray Mass Spectrometry and Surface Plasmon Resonance established supramolecular interactions (1:1 stoichiometry) between SCn and class S proteins in solution, but not class F proteins. The membrane binding affinity of S proteins ranged from KD = 0.07-6.2 nM. The binding ability was completely abolished by SCn at concentrations according to the number of benzenes (30-300 µM; SC8 < SC6 < SC4). The inhibitory properties of SCn 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.
Benoît-Joseph Laventie; Cristina Potrich; Cédric Atmanène; Maher Saleh; Olivier Joubert; Gabriella Viero; Christoph Bachmeyer; Valeria Antonini; Ines Mancini; Sarah Cianferani-Sanglier; Daniel Keller; Didier A Colin; Tristan Bourcier; Gregor Anderluh; Alain van Dorsselaer; Mauro Dalla Serra; Gilles Prévost
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-3
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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