Toxins 2018, 10(10), 385; https://doi.org/10.3390/toxins10100385
Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A
College of Veterinary Medicine, Sichuan Agriculture University, Chengdu 610000, China
†
These authors contributed equally.
*
Author to whom correspondence should be addressed.
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)
Abstract
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-TextKeywords:
sortase A; Staphylococcus aureus; erianin; inhibitor; molecular mechanism
▼
Figures
Figure 1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
Share & Cite This Article
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.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.