Development of Candida albicans Biofilms Is Diminished by Paeonia lactiflora via Obstruction of Cell Adhesion and Cell Lysis
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Candida albicans infections are often problematic to treat owing to antifungal resistance, as such infections are mostly associated with biofilms. The ability of C. albicans to switch from a budding yeast to filamentous hyphae and to adhere to host cells or various surfaces supports biofilm formation. Previously, the ethanol extract from Paeonia lactiflora was reported to inhibit cell wall synthesis and cause depolarization and permeabilization of the cell membrane in C. albicans. In this study, the P. lactiflora extract was found to significantly reduce the initial stage of C. albicans biofilms from 12 clinical isolates by 38.4%. Thus, to assess the action mechanism, the effect of the P. lactiflora extract on the adhesion of C. albicans cells to polystyrene and germ tube formation was investigated using a microscopic analysis. The density of the adherent cells was diminished following incubation with the P. lactiflora extract in an acidic medium. Additionally, the P. lactiflora-treated C. albicans cells were mostly composed of less virulent pseudohyphae, and ruptured debris was found in the serumcontaining medium. A quantitative real-time PCR analysis indicated that P. lactiflora downregulated the expression of C. albicans hypha-specific genes: ALS3 by 65% (p = 0.004), ECE1 by 34.9% (p = 0.001), HWP1 by 29.2% (p = 0.002), and SAP1 by 37.5% (p = 0.001), matching the microscopic analysis of the P. lactiflora action on biofilm formation. Therefore, the current findings demonstrate that the P. lactiflora ethanol extract is effective in inhibiting C. albicans biofilms in vitro, suggesting its therapeutic potential for the treatment of biofilmassociated infections.
Abstract
Candida albicans infections are often problematic to treat owing to antifungal resistance, as such infections are mostly associated with biofilms. The ability of C. albicans to switch from a budding yeast to filamentous hyphae and to adhere to host cells or various surfaces supports biofilm formation. Previously, the ethanol extract from Paeonia lactiflora was reported to inhibit cell wall synthesis and cause depolarization and permeabilization of the cell membrane in C. albicans. In this study, the P. lactiflora extract was found to significantly reduce the initial stage of C. albicans biofilms from 12 clinical isolates by 38.4%. Thus, to assess the action mechanism, the effect of the P. lactiflora extract on the adhesion of C. albicans cells to polystyrene and germ tube formation was investigated using a microscopic analysis. The density of the adherent cells was diminished following incubation with the P. lactiflora extract in an acidic medium. Additionally, the P. lactiflora-treated C. albicans cells were mostly composed of less virulent pseudohyphae, and ruptured debris was found in the serumcontaining medium. A quantitative real-time PCR analysis indicated that P. lactiflora downregulated the expression of C. albicans hypha-specific genes: ALS3 by 65% (p = 0.004), ECE1 by 34.9% (p = 0.001), HWP1 by 29.2% (p = 0.002), and SAP1 by 37.5% (p = 0.001), matching the microscopic analysis of the P. lactiflora action on biofilm formation. Therefore, the current findings demonstrate that the P. lactiflora ethanol extract is effective in inhibiting C. albicans biofilms in vitro, suggesting its therapeutic potential for the treatment of biofilmassociated infections.
참고문헌 (33)
- Pfaller MA, "Invasive fungal pathogens: current epidemiological trends", Clin. Infect. Dis., 43, pp.S3~S14 (2006)[DOI]
- Martinez LR, "Fungal biofilms: relevance in the setting of human disease", Curr. Fungal Infect. Rep., 4, pp.266~275 (2010)[DOI]
- Ramage G, "Candida biofilms on implanted biomaterials: a clinically significant problem", FEMS Yeast Res., 6, pp.979~986 (2006)[DOI]
- Ramage G, "Fungal biofilm resistance", Int. J. Microbiol., 2012, pp.1~14 (2012)
- Mathe L, "Recent insights into Candida albicans biofilm resistance mechanisms", Curr. Genet., 59, pp.251~264 (2013)
- Uppuluri P, "Dispersion as an important step in the Candida albicans biofilm developmental cycle", PLoS Pathog., 6, pp.e1000828~ (2010)[DOI]
- Mukherjee PK, "Mechanism of fluconazole resistance in Candida albicans biofilms: phase-specific role of efflux pumps and membrane sterols", Infect. Immun., 71, pp.4333~4340 (2003)[DOI]
- Campbell BC, "Chemosensitization as a means to augment commercial antifungal agents", Front. Microbiol., 3, pp.79~ (2012)
- Cowen LE, "The evolution of fungal drug resistance: modulating the trajectory from genotype to phenotype", Nat. Rev. Microbiol., 6, pp.187~198 (2008)[DOI]
- Bink A, "Anti-biofilm strategies: how to eradicate Candida biofilms?", Open Mycol. J., 5, pp.29~38 (2011)[DOI]
- 이흥식, "Paeonia lactiflora Inhibits Cell Wall Synthesis and Triggers Membrane Depolarization in Candida albicans", Journal of Microbiology and Biotechnology, 27(2), pp.395~404 (2017), 한국미생물·생명공학회[DOI]
- Su Jung Park, "Relationship between Biofilm Formation Ability and Virulence of Candida albicans", Journal of Bacteriology and Virology, 39(2), pp.119~124 (2009), 대한미생물학회
- Liu M, "Colorimetric broth microdilution method for the antifungal screening of plant extracts against yeast", Methods, 42, pp.325~329 (2007)[DOI]
- Chandra J, "Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance", J. Bacteriol., 183, pp.5385~5394 (2001)[DOI]
- Thein ZM, "In vitro biofilm formation of Candida albicans and non-albicans Candida species under dynamic and anaerobic conditions", Arch. Oral Biol., 52, pp.761~767 (2007)[DOI]
- Skrzypek MS, "The Candida Genome Database (CGD): incorporation of Assembly 22, systematic identifiers and visualization of high throughput sequencing data", Nucleic Acids Res., 45, pp.D592~D596 (2017)[DOI]
- Untergasser A, "Primer3 - new capabilities and interfaces", Nucleic Acids Res., 40, pp.e115~ (2012)[DOI]
- Kucharikova S, "Detailed comparison of Candida albicans and Candida glabrata biofilms under different conditions and their susceptibility to caspofungin and anidulafungin", J. Med. Microbiol., 60, pp.1261~1269 (2011)[DOI]
- Sudbery P, "The distinct morphogenic states of Candida albicans", Trends Microbiol., 12, pp.317~324 (2004)[DOI]
- Merson-Davies LA, "A morphology index for characterization of cell shape in Candida albicans", J. Gen. Microbiol., 135, pp.3143~3152 (1989)
- Hoyer LL, "The ALS gene family of Candida albicans", Trends Microbiol., 9, pp.176~180 (2001)[DOI]
- Li F, "Eap1p, an adhesin that mediates Candida albicans biofilm formation in vitro and in vivo", Eukaryot. Cell, 6, pp.931~939 (2007)[DOI]
- Moyes DL, "Candidalysin is a fungal peptide toxin critical for mucosal infection", Nat., 532, pp.64~68 (2016)[DOI]
- Sundstrom P, "Adhesion in Candida spp.", Cell. Microbiol., 4, pp.461~469 (2002)[DOI]
- Schaller M, "Hydrolytic enzymes as virulence factors of Candida albicans", Mycoses, 48, pp.365~377 (2005)[DOI]
- Schaller M, "Invasion of Candida albicans correlates with expression of secreted aspartic proteinases during experimental infection of human epidermis", J. Invest. Dermatol., 114, pp.712~717 (2000)[DOI]
- Silva S, "Candida glabrata, Candida parapsilosis and Candida tropicalis: biology, epidemiology, pathogenicity and antifungal resistance", FEMS Microbiol. Rev., 36, pp.288~305 (2012)[DOI]
- Gow NA, "Fungal morphogenesis and host invasion", Curr. Opin. Microbiol., 5, pp.366~371 (2002)[DOI]
- Thompson DS, "Coevolution of morphology and virulence in Candida species", Eukaryot. Cell, 10, pp.1173~1182 (2011)[DOI]
- Hoyer LL, "Candida albicans ALS1: domains related to a Saccharomyces cerevisiae sexual agglutinin separated by a repeating motif", Mol. Microbiol., 15, pp.39~54 (1995)[DOI]
- Hoyer LL, "Candida albicans ALS3 and insights into the nature of the ALS gene family", Curr. Genet., 33, pp.451~459 (1998)
- Rameau RD, "The human disease-associated <TEX>$A{\beta}$<", TEX> amyloid core sequence forms functional amyloids in a fungal adhesin, 2016, pp.7, e1815~e1815
- Ram sook CB, "Yeast cell adhesion molecules have functional amyloid-forming sequences", Eukaryot. Cell, 9, pp.393~404 (2010)[DOI]