Chandra J, Kuhn D M, Mukherjee P K, Hoyer L L, McCormick T, Ghannoum M A
Center for Medical Mycology, University Hospitals of Cleveland, and Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
J Bacteriol. 2001 Sep;183(18):5385-94. doi: 10.1128/JB.183.18.5385-5394.2001.
Biofilms are a protected niche for microorganisms, where they are safe from antibiotic treatment and can create a source of persistent infection. Using two clinically relevant Candida albicans biofilm models formed on bioprosthetic materials, we demonstrated that biofilm formation proceeds through three distinct developmental phases. These growth phases transform adherent blastospores to well-defined cellular communities encased in a polysaccharide matrix. Fluorescence and confocal scanning laser microscopy revealed that C. albicans biofilms have a highly heterogeneous architecture composed of cellular and noncellular elements. In both models, antifungal resistance of biofilm-grown cells increased in conjunction with biofilm formation. The expression of agglutinin-like (ALS) genes, which encode a family of proteins implicated in adhesion to host surfaces, was differentially regulated between planktonic and biofilm-grown cells. The ability of C. albicans to form biofilms contrasts sharply with that of Saccharomyces cerevisiae, which adhered to bioprosthetic surfaces but failed to form a mature biofilm. The studies described here form the basis for investigations into the molecular mechanisms of Candida biofilm biology and antifungal resistance and provide the means to design novel therapies for biofilm-based infections.
生物膜是微生物的一个受保护的生态位，在其中它们免受抗生素治疗的影响，并可成为持续性感染的来源。利用在生物假体材料上形成的两种临床相关的白色念珠菌生物膜模型，我们证明生物膜的形成经历三个不同的发育阶段。这些生长阶段将附着的芽生孢子转变为包裹在多糖基质中的明确细胞群落。荧光和共聚焦扫描激光显微镜显示，白色念珠菌生物膜具有由细胞和非细胞成分组成的高度异质结构。在两种模型中，生物膜生长的细胞的抗真菌耐药性随着生物膜的形成而增加。编码与粘附于宿主表面有关的一类蛋白质的凝集素样（ALS）基因的表达在浮游细胞和生物膜生长的细胞之间受到不同的调控。白色念珠菌形成生物膜的能力与酿酒酵母形成鲜明对比，酿酒酵母粘附于生物假体表面但未能形成成熟的生物膜。这里描述的研究为探究念珠菌生物膜生物学和抗真菌耐药性的分子机制奠定了基础，并为设计基于生物膜感染的新疗法提供了手段。
