Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence

• DOI: 10.1073/pnas.96.4.1218
• Publication Date: 2002-07-26T14:39:15Z
• Authors: Patricia Mayville; Guangyong Ji; Ronald Beavis; Hongmei Yang; Michael Goger; Richard P. Novick; Tom W. Muir
• Keywords: Thiolactone

The synthesis of virulence factors and other extracellular proteins responsible for pathogenicity in Staphylococcus aureus is under the control agr locus. A secreted agr-encoded peptide, AgrD, processed from AgrD gene product, known to be an effector self-strain activation cross-strain inhibition response. Biochemical analysis peptides isolated culture supernatants has suggested that they contain unusual thiol ester-linked cyclic structure. In present work, chemical used confirm mature a thiolactone structure this feature absolutely necessary full biological activity. synthetic exhibited activity vivo mouse protection test. Structure-activity studies have allowed key aspects peptide involved differential functions identified. Accordingly, we propose model response which former, but not latter, involves specific acylation transmembrane receptor, AgrC.