Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A
by
Ping Ouyang †, Xuewen He †, Zhong-Wei Yuan †, Zhong-Qiong Yin, Hualin Fu, Juchun Lin, Changliang He, Xiaoxia Liang, Cheng Lv, Gang Shu, Zhi-Xiang Yuan
, Xu Song, Lixia Li and Lizi Yin *
Ping Ouyang †, Xuewen He †, Zhong-Wei Yuan †, Zhong-Qiong Yin, Hualin Fu, Juchun Lin, Changliang He, Xiaoxia Liang, Cheng Lv, Gang Shu, Zhi-Xiang Yuan, Xu Song, Lixia Li and Lizi Yin *
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; https://doi.org/10.3390/toxins10100385
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.
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Keywords:
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.
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