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Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A

College of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, China
Author to whom correspondence should be addressed.
These authors contributed equally.
Toxins 2018, 10(10), 385;
Received: 7 August 2018 / Revised: 8 September 2018 / Accepted: 20 September 2018 / Published: 23 September 2018
(This article belongs to the Special Issue Staphylococcus aureus Toxins)
With continuous emergence and widespread of multidrug-resistant Staphylococcus aureus 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—IC50 = 20.91 ± 2.31 μg/mL, 65.7 ± 7.2 μM) at subminimum inhibitory concentrations (minimum inhibitory concentrations—MIC = 512 μg/mL against S. aureus). 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 S. aureus binding to fibronectin and biofilm formation were inhibited by erianin, when co-culture with S. aureus. In vivo, erianin could improve the survival in mice that infected with S. aureus by tail vein injection. Experimental results showed that erianin is a potential novel therapeutic compound against S. aureus infections via affecting srtA. View Full-Text
Keywords: sortase A; Staphylococcus aureus; erianin; inhibitor; molecular mechanism sortase A; Staphylococcus aureus; erianin; inhibitor; molecular mechanism
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MDPI and ACS Style

Ouyang, P.; He, X.; Yuan, Z.-W.; Yin, Z.-Q.; Fu, H.; Lin, J.; He, C.; Liang, X.; Lv, C.; Shu, G.; Yuan, Z.-X.; Song, X.; Li, L.; Yin, L. Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A. Toxins 2018, 10, 385.

AMA Style

Ouyang P, He X, Yuan Z-W, Yin Z-Q, Fu H, Lin J, He C, Liang X, Lv C, Shu G, Yuan Z-X, Song X, Li L, Yin L. Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A. Toxins. 2018; 10(10):385.

Chicago/Turabian Style

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. 2018. "Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A" Toxins 10, no. 10: 385.

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