Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/19/2005
Publication Date: 10/25/2005
Citation: Park, B-S., Kim, J-G., Kim, M-R., Lee, S-E., Takeoka, G.R., Oh, K-B., Kim, J-H. 2005. Curcuma longa L. Constituents Inhibit Sortase A and Staphylococcus aureus Cell Adhesion to Fibronectin. Journal of Agricultural and Food Chemistry, 53:9005-9009. Interpretive Summary: The use of plants and/or their constituents is generating much interest as alternatives to synthetic antibacterial agents. We have investigated the common spice, turmeric, and have identified three curcuminoids, curcumin, demthoxycurcumin and bisdemethoxycurcumin, which were found to be potent inhibitors of sortase A. It is believed that sortase A inhibitors act as anti-infective agents and disrupt the pathogenesis of bacterial infections without affecting microbial viability. We believe that curcumin has potential for the treatment of Staphylococcus aureus infections via inhibition of sortase A activity.
Technical Abstract: The inhibitory activity of Curcuma longa L. (turmeric) rhizome constituents against sortase A, a bacterial surface protein anchoring transpeptidase, from Staphylococcus aureus ATCC 6538p was evaluated. The activity of the isolated compounds (1-4) was compared to that of the positive control, p-hydroxymecuribenzoic acid (pHMB). The biologically active components of C. longa rhizome were characterized by spectroscopic analysis as the curcuminoids, curcumin (1), demethoxycurcumin (2), and bisdemethoxycurcumin (3). Curcumin was a potent inhibitor of sortase A, with an IC50 value of 13.8 ± 0.7 'g/mL. Bisdemethoxycurcumin (IC50 = 31.9 ± 1.2 'g/mL), and demethoxycurcumin (IC50 = 23.8 ± 0.6 'g/mL) were more effective than pHMB (IC50 = 40.6 ± 1.2 'g/mL). The three isolated compounds (1-3) showed no growth inhibitory activity against S. aureus strain Newman, with minimum inhibitory concentrations (MICs) greater than 200 'g/mL. Curcumin also exhibited potent inhibitory activity against S. aureus cell adhesion to fibronectin. The suppression of fibronectin-binding activity by curcumin highlights its potential for the treatment of S. aureus infections via inhibition of sortase activity. These results indicate that curcumin is a possible candidate in the development of a bacterial sortase A inhibitor.