Next Article in Journal
Terminamines K–S, Antimetastatic Pregnane Alkaloids from the Whole Herb of Pachysandra terminalis
Previous Article in Journal
Antiprotozoal and Antiglycation Activities of Sesquiterpene Coumarins from Ferula narthex Exudate
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Molecules 2016, 21(10), 1285; doi:10.3390/molecules21101285

Acacetin Protects Mice from Staphylococcus aureus Bloodstream Infection by Inhibiting the Activity of Sortase A

1
College of Animal Science, Jilin University, Changchun 130062, China
2
Department of Pharmacology, College of Basic Medical Science, Jilin University, Changchun 130062, China
3
College of Animal Science and Technology, Jilin Agricultural University, Changchun 130062, China
4
Key Laboratory of Zoonosis Research, Ministry of Education/Institute of Zoonosis/College of Veterinary Medicine, Jilin University, Changchun 130062, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 16 August 2016 / Revised: 20 September 2016 / Accepted: 22 September 2016 / Published: 26 September 2016
(This article belongs to the Section Medicinal Chemistry)
View Full-Text   |   Download PDF [9273 KB, uploaded 26 September 2016]   |  

Abstract

Staphylococcus aureus (S. aureus) is a major cause of infection in hospitals and communities. Widespread dissemination of multi-drug resistant S. aureus is a serious threat to the health of humans and animals. An anti-virulence strategy has been widely considered as an alternative therapeutic approach. Inhibitors of virulence factors are able to treat S. aureus infections without influencing the growth or viability of bacteria and rarely lead to bacterial resistance. Sortase A (SrtA) is a membrane-associated cysteine transpeptidase that catalyzes up to 25 surface proteins that covalently bind to cell wall peptidoglycans. In S. aureus, most of these surface proteins have been identified as important virulence factors that are vital in bacterial pathogenesis. In the present study, we show that acacetin, a natural flavonoid compound, inhibits the activity of SrtA in S. aureus (IC50 = 36.46 ± 4.69 μg/mL, 128 μM) which affects the assembly of protein A (SpA) to cell walls and reduces the binding of S. aureus to fibrinogen (Fg). The mechanism of the interaction between acacetin and SrtA were preliminarily discussed using molecular dynamics simulations. The results suggested that acacetin adopted a compact conformation binding at the pocket of the SrtA via residues Arg-139 and Lys-140. By performing an animal infection model, we demonstrated that acacetin was able to protect mice from renal abscess formation induced by S. aureus and significantly increased survival rates. Taken together, these findings suggest that acacetin may be a promising candidate for the development of anti-S. aureus drugs. View Full-Text
Keywords: Staphylococcus aureus; sortase A; acacetin; inhibitor; renal abscess Staphylococcus aureus; sortase A; acacetin; inhibitor; renal abscess
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).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Bi, C.; Dong, X.; Zhong, X.; Cai, H.; Wang, D.; Wang, L. Acacetin Protects Mice from Staphylococcus aureus Bloodstream Infection by Inhibiting the Activity of Sortase A. Molecules 2016, 21, 1285.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top