Effect of microbial siderophores on matrix metalloproteinase-2 activity.

Matrix metalloproteinases (MMPs) are capable of cleaving almost all macromolecules of the extracellular connective tissue matrix and are thought to play a major role in tissue destructive inflammatory diseases such as periodontitis. The aim of this study was to determine the effects of siderophores, which are iron-chelating molecules produced by a variety of microorganisms, on the activity of MMP-2. Heat-denatured type I collagen (gelatin) was incubated with p-aminophenylmercuric acetate-activated MMP-2 and siderophores. Degradation of gelatin was monitored by SDS-PAGE and Coomassie blue staining. Ferrichrome, rhodotorulic acid, desferoxamine mesylate and 2,3-dihydroxybenzoic acid were found to inhibit the MMP-2 activity whereas beta-phenylpyruvic acid had no effect. The inhibition could be reversed by adding an excess calcium chloride or ferric chloride to the assay mixtures. Our study suggests that microbial siderophores may represent new-potential therapeutic molecules for the treatment of destructive inflammatory diseases involving excess MMP-2 activity, such as periodontitis.