Ells Ruan, Kock Johan L F, Van Wyk Pieter W J, Botes Piet J, Pohl Carolina H
Department of Microbial, Biochemical and Food Biotechnology, University of the Free State, PO Box 339, Bloemfontein 9300, South Africa.
J Antimicrob Chemother. 2009 Jan;63(1):124-8. doi: 10.1093/jac/dkn446. Epub 2008 Oct 29.
During Candida albicans infection, arachidonic acid (AA) is released from phospholipids of infected host cell membranes and used by C. albicans as the sole carbon source and for production of eicosanoids. AA can be incorporated into the phospholipids of yeasts, influencing the saturation level and fluidity of yeast cell membranes. It is suggested that the effectiveness of polyene (e.g. amphotericin B) and imidazole (e.g. clotrimazole) antifungals may depend upon the level of unsaturation and ergosterol in the membrane. Therefore, the aim of this study was to evaluate the effect of AA on the cell membrane and susceptibility of C. albicans and Candida dubliniensis biofilms towards amphotericin B and clotrimazole.
Both yeasts were grown in the presence and absence of AA and the effect of amphotericin B and clotrimazole was examined by confocal laser scanning microscopy, determination of mitochondrial metabolism, unsaturation index of the phospholipid fractions and ergosterol content of the membranes.
AA had no effect on the viability of the cells in the biofilm; however, there was an increase in ergosterol levels as well as antifungal susceptibility of biofilms grown in the presence of AA.
AA influences phospholipid unsaturation and ergosterol content of both yeasts C. albicans and C. dublininensis, increasing susceptibility towards the antifungals. Pretreatment of biofilms with polyunsaturated fatty acids may result in the reduction in antifungal dose needed to inhibit biofilms.
在白色念珠菌感染过程中,花生四烯酸(AA)从受感染宿主细胞膜的磷脂中释放出来,被白色念珠菌用作唯一碳源并用于合成类二十烷酸。AA可掺入酵母的磷脂中,影响酵母细胞膜的饱和度和流动性。有人提出,多烯类(如两性霉素B)和咪唑类(如克霉唑)抗真菌药的有效性可能取决于膜中不饱和程度和麦角固醇的水平。因此,本研究的目的是评估AA对白色念珠菌和都柏林念珠菌生物膜细胞膜的影响以及它们对两性霉素B和克霉唑的敏感性。
两种酵母均在有或无AA的情况下培养,通过共聚焦激光扫描显微镜、线粒体代谢测定、磷脂组分的不饱和指数以及膜中麦角固醇含量来检测两性霉素B和克霉唑的作用。
AA对生物膜中细胞的活力没有影响;然而,在有AA存在的情况下生长的生物膜中,麦角固醇水平以及抗真菌敏感性有所增加。
AA影响白色念珠菌和都柏林念珠菌这两种酵母的磷脂不饱和程度和麦角固醇含量,增加它们对抗真菌药的敏感性。用多不饱和脂肪酸对生物膜进行预处理可能会降低抑制生物膜所需的抗真菌剂量。