Department of Biology and South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio, San Antonio, Texas, United States of America.
PLoS Pathog. 2010 Mar 26;6(3):e1000828. doi: 10.1371/journal.ppat.1000828.
Biofilms are dynamic microbial communities in which transitions between planktonic and sessile modes of growth occur interchangeably in response to different environmental cues. In the last decade, early events associated with C. albicans biofilm formation have received considerable attention. However, very little is known about C. albicans biofilm dispersion or the mechanisms and signals that trigger it. This is important because it is precisely C. albicans cells dispersed from biofilms that are the main culprits associated with candidemia and establishment of disseminated invasive disease, two of the gravest forms of candidiasis. Using a simple flow biofilm model recently developed by our group, we have performed initial investigations into the phenomenon of C. albicans biofilm dispersion, as well as the phenotypic characteristics associated with dispersed cells. Our results indicate that C. albicans biofilm dispersion is dependent on growing conditions, including carbon source and pH of the media used for biofilm development. C. albicans dispersed cells are mostly in the yeast form and display distinct phenotypic properties compared to their planktonic counterparts, including enhanced adherence, filamentation, biofilm formation and, perhaps most importantly, increased pathogenicity in a murine model of hematogenously disseminated candidiasis, thus indicating that dispersed cells are armed with a complete arsenal of "virulence factors" important for seeding and establishing new foci of infection. In addition, utilizing genetically engineered strains of C. albicans (tetO-UME6 and tetO-PES1) we demonstrate that C. albicans biofilm dispersion can be regulated by manipulating levels of expression of these key genes, further supporting the evidence for a strong link between biofilms and morphogenetic conversions at different stages of the C. albicans biofilm developmental cycle. Overall, our results offer novel and important insight into the phenomenon of C. albicans biofilm dispersion, a key part of the biofilm developmental cycle, and provide the basis for its more detailed analysis.
生物膜是动态的微生物群落,其中浮游和静止生长模式之间的转换会根据不同的环境线索相互交替发生。在过去的十年中,与白色念珠菌生物膜形成相关的早期事件引起了相当大的关注。然而,对于白色念珠菌生物膜的分散或触发它的机制和信号知之甚少。这很重要,因为正是从生物膜中分散出来的白色念珠菌细胞是与念珠菌血症和播散性侵袭性疾病(念珠菌病最严重的两种形式)相关的主要罪魁祸首。使用我们小组最近开发的一种简单的流动生物膜模型,我们对白色念珠菌生物膜分散的现象以及与分散细胞相关的表型特征进行了初步研究。我们的结果表明,白色念珠菌生物膜的分散取决于生长条件,包括用于生物膜形成的碳源和培养基的 pH 值。白色念珠菌分散的细胞主要呈酵母形态,与浮游细胞相比表现出明显的表型特征,包括增强的黏附性、菌丝形成、生物膜形成,也许最重要的是,在血液播散性念珠菌病的小鼠模型中增加了致病性,这表明分散的细胞拥有一整套“毒力因子”,对于播种和建立新的感染灶非常重要。此外,利用白色念珠菌的遗传工程菌株(tetO-UME6 和 tetO-PES1),我们证明可以通过操纵这些关键基因的表达水平来调节白色念珠菌生物膜的分散,进一步支持了生物膜与不同阶段白色念珠菌生物膜发育周期的形态发生转换之间存在强关联的证据。总的来说,我们的研究结果为白色念珠菌生物膜分散这一现象提供了新的重要见解,这是生物膜发育周期的关键部分,为其更详细的分析提供了基础。