Isovitexin, a Potential Candidate Inhibitor of Sortase A of Staphylococcus aureus USA300

Abstract

Staphylococcus aureus causes a broad variety of diseases. The spread of multidrug-resistant S. aureus highlights the need to develop new ways to combat S. aureus infections. Sortase A (SrtA) can anchor proteins containing LPXTG binding motifs to the bacteria surface and plays a key role in S. aureus infections, making it a promising antivirulence target. In the present study, we used a SrtA activity inhibition assay to discover that isovitexin, a Chinese herbal product, can inhibit SrtA activity with an IC 5 0 of 28.98 µg/ml. Using a fibrinogen-binding assay and a biofilm formation assay, we indirectly proved the SrtA inhibitory activity of isovitexin. Additionally, isovitexin treatment decreased the amount of staphylococcal protein A (SpA) on the surface of the cells. These data suggest that isovitexin has the potential to be an anti-infective drug against S. aureus via the inhibition of sortase activity.

Developing natural products as potential anti-biofilm agents

“…Recently, emerging evidences also indicated that natural products such as erianin (from Dendrobium chrysotoxum), isovitexin and parthenolide exhibited inhibitory effect on cell adhesion, binding activity of fibronectin and QS factors respectively through targeting SrtA or downregulation of surface protein staphylococcal protein A (SpA) or blocking P. aeruginosa associated virulence factors, thereby impairing microbial biofilm formation [60][61][62].…”

Phytochemical Composition and In Vitro Biological Activity of Iris spp. (Iridaceae): A New Source of Bioactive Constituents for the Inhibition of Oral Bacterial Biofilms

“…Interestingly, flavonoids exhibited strong sortase inhibitory activity, which is an enzyme that is responsible for modulating the attachment ability of cells to host tissue and the production of surface protein virulence factors to the peptidoglycan cell wall layer of Gram-positive bacteria such as Streptococcus mutans and Streptococcus pneumoniae [ 38 , 40 ]. The inhibitory effect on the S. aureus sortase A activity of the dryocrassin ABBA flavonoid has been studied [ 41 ], and similar activity was also observed with the application of isovitexin at an IC 50 of 28.98 mg/L [ 42 ]. Therefore, it is conceivable that the anti-biofilm potential of the extracts may be related to the ability of their phytochemical components to inactivate bacterial adhesins and enzymes altering the cell membrane, cell–substratum interactions, adherence phase, and biofilm maturation.…”

Inhibitory effect of a natural phenolic compound, 3-p-trans-coumaroyl-2-hydroxyquinic acid against the attachment phase of biofilm formation of Staphylococcus aureus through targeting sortase A

“…These results were consistent with previous studies that reported many natural products exerted inhibitory effect on the adhesion of S. aureus to brinogen. 2,23,38,39 Hence, it can be inferred that CHQA might inhibit the attachment phase of biolm formation by affecting the adhesion of S. aureus to host surface, eventually lead to weak biolm formation.…”

“…Numerous polyphenols have been demonstrated to signicantly inhibit the biolm formation of pathogens, 19,20 and many of them showed a potent inhibitory activity against SrtA of S. aureus, such as morin, myricetin, quercetin, 21 chlorogenic acid, 22 kaempferol, 10 and isovitexin. 23 Previously, we have reported a novel phenolic compound, 3-ptrans-coumaroyl-2-hydroxyquinic acid (CHQA, Fig. 1A) from pine needles of Cedrus deodara, which exhibited strong antibacterial activity against S. aureus through damaging bacterial cell membrane and disturbing cellular functions.…”