Curcuma longa L. Constituents Inhibit Sortase A and Staphylococcus aureus Cell Adhesion to Fibronectin

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 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.

Sortase as a Target of Anti-Infective Therapy

“…Measurements of bacterial adherence to fibronectin are not a direct measurement of sortase activity, and these assays suffer from pitfalls associated with inhibition of other pathways that also effect adherence (e.g., inhibition of protein synthesis or secretion of polypeptide through the Sec secretion pathway). Curcumin and derivatives from Curcuma longa also inhibited sortase with appreciable activity (IC 50 13-32 g/ml) and potentially prevented adherence to fibronectin (Park et al, 2005). In similar fashion, inhibitors of SrtB from S. aureus were isolated from the bark of the plant R. verniciflua.…”

Curcumin suppresses Streptococcus mutans adherence to human tooth surfaces and extracellular matrix proteins

“…Physical inhibition using the analogue contributes to preventing bacterial adhesion and dental diseases without any side effects, whereas other drugs, having bactericidal activity, eliminate both pathogenic and beneficial bacteria [21]. In addition, it was previously shown that curcumin did not affect the viability of the S. aureus strain Newman, but inhibited microbial adhesion to cell surfaces, suggesting a role as a potential preventive and curative agent of pathogenic bacterial infections [22]. Therefore, curcumin can be suggested as an improved therapeutic agent showing anti-adherence-based inhibitory mechanisms against S. mutans rather than bactericidal effects.…”

“…According to Park et al, Curcuma longa L. components impeded cell membrane-anchored sortase A (SrtA), which is responsible for controlling bacterial adherence to host tissues via interaction with cell-wall matrix proteins, resulting in the inhibition of S. aureus attachment to fibronectin via fibronectin-binding protein [22]. Hence, the use of an SrtA inhibitor such as curcumin was thought to have the potential to eliminate Gram-positive bacterial infections [22]. In addition, S. aureus mutants defective in sortase activity stopped exhibiting surface proteins and initiating infections without the bacterial growth being disturbed [26,27].…”

Chemopreventive Potential of an Ethyl Acetate Fraction from Curcuma Longa is Associated with Upregulation of p57kip2and Rad9 in the PC-3M Prostate Cancer Cell Line

“…Turmeric is traditionally known as a blood purifier and is reported to be useful for the common cold, intermittent fevers, afflictions of the liver, indolent ulcer and wound healing. It has been found to possess anti-inflammatory and antioxidant activities and chemopreventive activity for a wide variety of cancers like colon, breast, prostate, esophagus, lung, oral and has potential as an antiviral and antibacterial agent (Mazumder et al, 1995;Anto et al, 1996;Aggarwal et al, 2003;Dorai & Aggarwal, 2004;Duvoix et al, 2005;Olszanecki et al, 2005;Park et al, 2005;Alpers, 2008). Recently Aggarwal and co-workers using a commercially available curcumin mix reported that different analogs of curcumin present in turmeric showed variable anti-inflammatory and antiproliferative activities (Sandur et al, 2007).…”