Curcuma longa L. constituents inhibit sortase A and Staphylococcus aureus cell adhesion to fibronectin.
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 microg/mL. Bisdemethoxycurcumin (IC50 = 31.9 +/- 1.2 microg/mL) and demethoxycurcumin (IC50 = 23.8 +/- 0.6 microg/mL) were more effective than pHMB (IC50 = 40.6 +/- 1.2 microg/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 microg/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.
Park
Byeoung-Soo
BS
School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, South Korea.
Kim
Jae-Gyu
JG
Kim
Mi-Ran
MR
Lee
Sung-Eun
SE
Takeoka
Gary R
GR
Oh
Ki-Bong
KB
Kim
Jeong-Han
JH
D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors*; D001422:Bacterial Adhesion / Q000187:drug effects*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000302:isolation & purification / Q000494:pharmacology; D003546:Cysteine Endopeptidases; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism*; D027343:Rhizome / Q000737:chemistry; D013211:Staphylococcus aureus / Q000201:enzymology*
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D005353:Fibronectins; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases; D003474:Curcumin