Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A

• Published in: Toxins 2018-09, Vol.10 (10), p.385
• Main Authors: Ouyang, Ping, He, Xuewen, Yuan, Zhong-Wei, Yin, Zhong-Qiong, Fu, Hualin, Lin, Juchun, He, Changliang, Liang, Xiaoxia, Lv, Cheng, Shu, Gang, Yuan, Zhi-Xiang, Song, Xu, Li, Lixia, Yin, Lizi
• Format: Article
• Language: English
• Subjects: Aminoacyltransferases - antagonists & inhibitors; Aminoacyltransferases - metabolism; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Bacterial Adhesion - drug effects; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - metabolism; Bibenzyls - pharmacology; Bibenzyls - therapeutic use; Biofilms - drug effects; Cysteine Endopeptidases - metabolism; erianin; Fibrinogen - metabolism; inhibitor; Mice, Inbred BALB C; Molecular Docking Simulation; molecular mechanism; sortase A; Staphylococcal Infections - drug therapy; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - physiology
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins10100385

With continuous emergence and widespread of multidrug-resistant infections, common antibiotics have become ineffective in treating these infections in the clinical setting. Anti-virulence strategies could be novel, effective therapeutic strategies against drug-resistant bacterial infections. Sortase A (srtA), a transpeptidase in gram-positive bacteria, can anchor surface proteins that play a vital role in pathogenesis of these bacteria. SrtA is known as a potential antivirulent drug target to treat bacterial infections. In this study, we found that erianin, a natural bibenzyl compound, could inhibit the activity of srtA in vitro (half maximal inhibitory concentration-IC = 20.91 ± 2.31 μg/mL, 65.7 ± 7.2 μM) at subminimum inhibitory concentrations (minimum inhibitory concentrations-MIC = 512 μg/mL against ). The molecular mechanism underlying the inhibition of srtA by erianin was identified using molecular dynamics simulation: erianin binds to srtA residues Ile182, Val193, Trp194, Arg197, and Ile199, forming a stable bond via hydrophobic interactions. In addition, the activities of binding to fibronectin and biofilm formation were inhibited by erianin, when co-culture with . In vivo, erianin could improve the survival in mice that infected with by tail vein injection. Experimental results showed that erianin is a potential novel therapeutic compound against infections via affecting srtA.