Myricetin Protects Galleria Mellonella Against Staphylococcus Aureus Infection and Inhibits Multiple Virulence Factors

Overview

Journal Sci Rep

Specialty Science

Date 2017 Jun 8

PMID 28588273

Citations 41

Authors

L N Silva

G C A Da Hora

T A Soares

M S Bojer

H Ingmer

A J Macedo

D S Trentin

Affiliations

Soon will be listed here.

Abstract

Staphylococcus aureus is an opportunistic pathogen related to a variety of life-threatening infections but for which antimicrobial resistance is liming the treatment options. We report here that myricetin, but not its glycosylated form, can remarkably decrease the production of several S. aureus virulence factors, including adhesion, biofilm formation, hemolysis and staphyloxanthin production, without interfering with growth. Myricetin affects both surface proteins and secreted proteins which indicate that its action is unrelated to inhibition of the agr quorum sensing system. Analysis of virulence related gene expression and computational simulations of pivotal proteins involved in pathogenesis demonstrate that myricetin downregulates the saeR global regulator and interacts with sortase A and α-hemolysin. Furthermore, Myr confers a significant degree of protection against staphylococcal infection in the Galleria mellonella model. The present findings reveal the potential of Myr as an alternative multi-target antivirulence candidate to control S. aureus pathogenicity.

Citing Articles

Intraspecific cooperation allows the survival of Staphylococcus aureus staff: a novel strategy for disease relapse.

Luo H, Ni L, Chen T, Huang L, Zhang X, Li X BMC Infect Dis. 2024; 24(1):1092.

PMID: 39354412 PMC: 11445958. DOI: 10.1186/s12879-024-10001-2.

Optimization of Experimental Infection of the Animal Model Linnaeus 1758 (Lepidoptera: Pyralidae) with the Gram-Positive Bacterium .

Banfi D, Bianchi T, Mastore M, Brivio M Insects. 2024; 15(8).

PMID: 39194822 PMC: 11354611. DOI: 10.3390/insects15080618.

Myricetin Acts as an Inhibitor of Type II NADH Dehydrogenase from .

Zhou J, Chen H, Xu J, Huang M, Wang J, Shen H Molecules. 2024; 29(10).

PMID: 38792214 PMC: 11124336. DOI: 10.3390/molecules29102354.

Synthesis and study of antibiofilm and antivirulence properties of flavonol analogues generated by palladium catalyzed ligand free Suzuki-Miyaura coupling against PAO1.

Benny A, Thamim M, Srivastava P, Suresh S, Thirumoorthy K, Rangasamy L RSC Adv. 2024; 14(18):12278-12293.

PMID: 38633488 PMC: 11019961. DOI: 10.1039/d3ra08617h.

biofilm: Formulation, regulatory, and emerging natural products-derived therapeutics.

Wu X, Wang H, Xiong J, Yang G, Hu J, Zhu Q Biofilm. 2024; 7:100175.

PMID: 38298832 PMC: 10827693. DOI: 10.1016/j.bioflm.2023.100175.

References

Trentin D, Silva D, Amaral M, Zimmer K, Silva M, Lopes N . Tannins possessing bacteriostatic effect impair Pseudomonas aeruginosa adhesion and biofilm formation. PLoS One. 2013; 8(6):e66257. PMC: 3679062. DOI: 10.1371/journal.pone.0066257. View

Ong K, Khoo H . Biological effects of myricetin. Gen Pharmacol. 1997; 29(2):121-6. DOI: 10.1016/s0306-3623(96)00421-1. View

Krasowska A, Sigler K . How microorganisms use hydrophobicity and what does this mean for human needs?. Front Cell Infect Microbiol. 2014; 4:112. PMC: 4137226. DOI: 10.3389/fcimb.2014.00112. View

Lowy F . Staphylococcus aureus infections. N Engl J Med. 1998; 339(8):520-32. DOI: 10.1056/NEJM199808203390806. View

Novick R, Geisinger E . Quorum sensing in staphylococci. Annu Rev Genet. 2008; 42:541-64. DOI: 10.1146/annurev.genet.42.110807.091640. View

Yang Z, Xiong K, Qi P, Yang Y, Tu Q, Wang J . Gallic acid tailoring surface functionalities of plasma-polymerized allylamine-coated 316L SS to selectively direct vascular endothelial and smooth muscle cell fate for enhanced endothelialization. ACS Appl Mater Interfaces. 2014; 6(4):2647-56. DOI: 10.1021/am405124z. View

Otto M . Staphylococcus aureus toxins. Curr Opin Microbiol. 2014; 17:32-7. PMC: 3942668. DOI: 10.1016/j.mib.2013.11.004. View

Liu C, Liu G, Song Y, Yin F, Hensler M, Jeng W . A cholesterol biosynthesis inhibitor blocks Staphylococcus aureus virulence. Science. 2008; 319(5868):1391-4. PMC: 2747771. DOI: 10.1126/science.1153018. View

Cegelski L, Marshall G, Eldridge G, Hultgren S . The biology and future prospects of antivirulence therapies. Nat Rev Microbiol. 2007; 6(1):17-27. PMC: 2211378. DOI: 10.1038/nrmicro1818. View

10.

Bhakdi S, Tranum-Jensen J . Alpha-toxin of Staphylococcus aureus. Microbiol Rev. 1991; 55(4):733-51. PMC: 372845. DOI: 10.1128/mr.55.4.733-751.1991. View

11.

Berube B, Bubeck Wardenburg J . Staphylococcus aureus α-toxin: nearly a century of intrigue. Toxins (Basel). 2013; 5(6):1140-66. PMC: 3717774. DOI: 10.3390/toxins5061140. View

12.

Liu G, Essex A, Buchanan J, Datta V, Hoffman H, Bastian J . Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity. J Exp Med. 2005; 202(2):209-15. PMC: 2213009. DOI: 10.1084/jem.20050846. View

13.

Benton B, Zhang J, Bond S, Pope C, Christian T, Lee L . Large-scale identification of genes required for full virulence of Staphylococcus aureus. J Bacteriol. 2004; 186(24):8478-89. PMC: 532413. DOI: 10.1128/JB.186.24.8478-8489.2004. View

14.

Arita-Morioka K, Yamanaka K, Mizunoe Y, Ogura T, Sugimoto S . Novel strategy for biofilm inhibition by using small molecules targeting molecular chaperone DnaK. Antimicrob Agents Chemother. 2014; 59(1):633-41. PMC: 4291377. DOI: 10.1128/AAC.04465-14. View

15.

Cheng A, McAdow M, Kim H, Bae T, Missiakas D, Schneewind O . Contribution of coagulases towards Staphylococcus aureus disease and protective immunity. PLoS Pathog. 2010; 6(8):e1001036. PMC: 2916881. DOI: 10.1371/journal.ppat.1001036. View

16.

Trentin D, Silva D, Frasson A, Rzhepishevska O, da Silva M, Pulcini E . Natural Green coating inhibits adhesion of clinically important bacteria. Sci Rep. 2015; 5:8287. PMC: 4319173. DOI: 10.1038/srep08287. View

17.

Dong J, Qiu J, Zhang Y, Lu C, Dai X, Wang J . Oroxylin A inhibits hemolysis via hindering the self-assembly of α-hemolysin heptameric transmembrane pore. PLoS Comput Biol. 2013; 9(1):e1002869. PMC: 3547825. DOI: 10.1371/journal.pcbi.1002869. View

18.

Desbois A, Coote P . Utility of Greater Wax Moth Larva (Galleria mellonella) for Evaluating the Toxicity and Efficacy of New Antimicrobial Agents. Adv Appl Microbiol. 2012; 78:25-53. DOI: 10.1016/B978-0-12-394805-2.00002-6. View

19.

Chan A, Wereszczynski J, Amer B, Yi S, Jung M, McCammon J . Discovery of Staphylococcus aureus sortase A inhibitors using virtual screening and the relaxed complex scheme. Chem Biol Drug Des. 2013; 82(4):418-28. PMC: 3841297. DOI: 10.1111/cbdd.12167. View

20.

Bischoff M, Dunman P, Kormanec J, Macapagal D, Murphy E, Mounts W . Microarray-based analysis of the Staphylococcus aureus sigmaB regulon. J Bacteriol. 2004; 186(13):4085-99. PMC: 421609. DOI: 10.1128/JB.186.13.4085-4099.2004. View