Effect of Shikonin Against Biofilms

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2019 Jun 4

PMID 31156594

Citations 36

Authors

Yu Yan

Fei Tan

Hao Miao

Hui Wang

Yingying Cao

Affiliations

Soon will be listed here.

Abstract

Candidiasis is often associated with the formation of biofilms. biofilms are inherently resistant to many clinical antifungal agents and have increasingly been found to be the sources of infections. Novel antifungal agents against biofilms are urgently needed. The aim of this study was to investigate the effect of shikonin (SK) against biofilms and to clarify the underlying mechanisms. XTT reduction assay showed that SK could not only inhibit the formation of biofilms but also destroy the maintenance of mature biofilms. In a mouse vulvovaginal candidiasis (VVC) model, the fungal burden was remarkably reduced upon SK treatment. Further study showed that SK could inhibit hyphae formation and reduce cellular surface hydrophobicity (CSH). Real-time reverse transcription-PCR analysis revealed that several hypha- and adhesion-specific genes were differentially expressed in SK-treated biofilm, including the downregulation of ECE1, HWP1, EFG1, CPH1, RAS1, ALS1, ALS3, CSH1 and upregulation of TUP1, NRG1, BCR1. Moreover, SK induced the production of farnesol, a quorum sensing molecule, and exogenous addition of farnesol enhanced the antibiofilm activity of SK. Taken together, these results indicated that SK could be a favorable antifungal agent in the clinical management of biofilms.

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References

Nobile C, Andes D, Nett J, Smith F, Yue F, Phan Q . Critical role of Bcr1-dependent adhesins in C. albicans biofilm formation in vitro and in vivo. PLoS Pathog. 2006; 2(7):e63. PMC: 1487173. DOI: 10.1371/journal.ppat.0020063. View

Miao H, Zhao L, Li C, Shang Q, Lu H, Fu Z . Inhibitory effect of Shikonin on Candida albicans growth. Biol Pharm Bull. 2012; 35(11):1956-63. DOI: 10.1248/bpb.b12-00338. View

Tronchin G, Pihet M, Lopes-Bezerra L, Bouchara J . Adherence mechanisms in human pathogenic fungi. Med Mycol. 2008; 46(8):749-72. DOI: 10.1080/13693780802206435. View

Ramage G, Saville S, Wickes B, Lopez-Ribot J . Inhibition of Candida albicans biofilm formation by farnesol, a quorum-sensing molecule. Appl Environ Microbiol. 2002; 68(11):5459-63. PMC: 129887. DOI: 10.1128/AEM.68.11.5459-5463.2002. View

Liu N, Zhong H, Tu J, Jiang Z, Jiang Y, Jiang Y . Discovery of simplified sampangine derivatives as novel fungal biofilm inhibitors. Eur J Med Chem. 2017; 143:1510-1523. DOI: 10.1016/j.ejmech.2017.10.043. View

Cordeiro R, Teixeira C, Brilhante R, Castelo-Branco D, Paiva M, Giffoni Leite J . Minimum inhibitory concentrations of amphotericin B, azoles and caspofungin against Candida species are reduced by farnesol. Med Mycol. 2012; 51(1):53-9. DOI: 10.3109/13693786.2012.692489. View

Braun B, Johnson A . Control of filament formation in Candida albicans by the transcriptional repressor TUP1. Science. 1997; 277(5322):105-9. DOI: 10.1126/science.277.5322.105. View

Anderson J . Evolution of antifungal-drug resistance: mechanisms and pathogen fitness. Nat Rev Microbiol. 2005; 3(7):547-56. DOI: 10.1038/nrmicro1179. View

Liu H, Kohler J, Fink G . Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science. 1994; 266(5191):1723-6. DOI: 10.1126/science.7992058. View

10.

Sasaki K, Abe H, Yoshizaki F . In vitro antifungal activity of naphthoquinone derivatives. Biol Pharm Bull. 2002; 25(5):669-70. DOI: 10.1248/bpb.25.669. View

11.

Braun B, Johnson A . TUP1, CPH1 and EFG1 make independent contributions to filamentation in candida albicans. Genetics. 2000; 155(1):57-67. PMC: 1461068. DOI: 10.1093/genetics/155.1.57. View

12.

Chen X, Yang L, Oppenheim J, Howard M . Cellular pharmacology studies of shikonin derivatives. Phytother Res. 2002; 16(3):199-209. DOI: 10.1002/ptr.1100. View

13.

Gimeno C, Ljungdahl P, Styles C, Fink G . Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS. Cell. 1992; 68(6):1077-90. DOI: 10.1016/0092-8674(92)90079-r. View

14.

Gulati M, Nobile C . Candida albicans biofilms: development, regulation, and molecular mechanisms. Microbes Infect. 2016; 18(5):310-21. PMC: 4860025. DOI: 10.1016/j.micinf.2016.01.002. View

15.

Li D, Zhao L, Mylonakis E, Hu G, Zou Y, Huang T . In vitro and in vivo activities of pterostilbene against Candida albicans biofilms. Antimicrob Agents Chemother. 2014; 58(4):2344-55. PMC: 4023736. DOI: 10.1128/AAC.01583-13. View

16.

Donlan R, Costerton J . Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev. 2002; 15(2):167-93. PMC: 118068. DOI: 10.1128/CMR.15.2.167-193.2002. View

17.

Mukherjee P, Long L, Kim H, Ghannoum M . Amphotericin B lipid complex is efficacious in the treatment of Candida albicans biofilms using a model of catheter-associated Candida biofilms. Int J Antimicrob Agents. 2008; 33(2):149-53. DOI: 10.1016/j.ijantimicag.2008.07.030. View

18.

Nam K, Son M, Park J, Lee E . Shikonins attenuate microglial inflammatory responses by inhibition of ERK, Akt, and NF-kappaB: neuroprotective implications. Neuropharmacology. 2008; 55(5):819-25. DOI: 10.1016/j.neuropharm.2008.06.065. View

19.

Kucharikova S, Sharma N, Spriet I, Maertens J, Van Dijck P, Lagrou K . Activities of systemically administered echinocandins against in vivo mature Candida albicans biofilms developed in a rat subcutaneous model. Antimicrob Agents Chemother. 2013; 57(5):2365-8. PMC: 3632894. DOI: 10.1128/AAC.02288-12. View

20.

Liao Z, Yan Y, Dong H, Zhu Z, Jiang Y, Cao Y . Endogenous nitric oxide accumulation is involved in the antifungal activity of Shikonin against Candida albicans. Emerg Microbes Infect. 2016; 5(8):e88. PMC: 5034102. DOI: 10.1038/emi.2016.87. View