Dispersion as an important step in the Candida albicans biofilm developmental cycle.
Dispersion as an important step in the Candida albicans biofilm developmental cycle.
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DOI：
10.1371/journal.ppat.1000828
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发表时间：
2010-03-26
期刊：
影响因子：
6.7
通讯作者：
Lopez-Ribot JL
中科院分区：
文献类型：
--
作者：
Uppuluri P;Chaturvedi AK;Srinivasan A;Banerjee M;Ramasubramaniam AK;Köhler JR;Kadosh D;Lopez-Ribot JL
生物膜是动态的微生物群落，其中浮游和固着生长模式之间的转变根据不同的环境线索交替发生。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受到了相当多的关注。然而，人们对白色念珠菌生物膜分散或触发它的机制和信号知之甚少。这一点很重要，因为从生物膜中分散的白色念珠菌细胞正是与念珠菌血症和播散性侵袭性疾病（念珠菌病的两种最严重形式）相关的罪魁祸首。使用我们小组最近开发的简单流动生物膜模型，我们对白色念珠菌生物膜分散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，白色念珠菌生物膜分散取决于生长条件，包括碳源和用于生物膜形成的介质的 pH 值。白色念珠菌分散细胞大多呈酵母形式，与浮游细胞相比，表现出不同的表型特性，包括增强的粘附性、丝状化、生物膜形成，以及也许最重要的是，在血行播散性念珠菌病鼠模型中致病性增加，从而表明分散的细胞配备了完整的“毒力因子”库，对于播种和建立新的感染灶很重要。此外，利用白色念珠菌的基因工程菌株（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分散，进一步支持了白色念珠菌生物膜发育周期不同阶段的生物膜和形态发生转换之间存在密切联系的证据。总体而言，我们的结果为白色念珠菌生物膜分散现象（生物膜发育周期的关键部分）提供了新颖且重要的见解，并为其更详细的分析提供了基础。 白色念珠菌是念珠菌病的主要病原体，念珠菌病是一种难以治疗的感染，主要发生在严重免疫抑制和其他高危患者中。念珠菌病通常与宿主表面和/或可植入医疗设备（尤其是血管内导管）上生物膜（封装在保护基质内的附着微生物群落）的形成有关。近年来，对于白色念珠菌来说，生物膜的形成过程备受关注。然而，生物膜分散（细胞从生物膜中释放）却并非如此。这很重要，因为这些分散的细胞是随后在远端器官建立播散性念珠菌病的原因。在这里，我们利用我们小组最近描述的流动条件下的生物膜形成模型来研究和表征白色念珠菌生物膜分散的现象。我们的结果表明，分散发生在生物膜发育周期的所有不同阶段，并且受到营养和其他理化条件的影响，而不是最终阶段的过程。此外，我们的研究结果为如何在分子水平上调控这一过程提供了初步见解。我们还证明，分散的细胞表现出与毒力增加相关的独特表型特性，具有重要的临床影响。
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. Candida albicans is the main causative agent of candidiasis, a difficult-to-treat infection that occurs mostly in severely immunosuppressed and other at-risk patients. Candidiasis is often associated with the formation of biofilms (attached microbial communities encapsulated within a protective matrix) on host surfaces and/or implantable medical devices, most notably intravascular catheters. In recent years, for C. albicans, the process of biofilm formation has received much attention. However, the same is not true for biofilm dispersion (the release of cells from the biofilm). This is important since these dispersed cells are responsible for the subsequent establishment of disseminated candidiasis at distal organs. Here we have taken advantage of a model of biofilm formation under conditions of flow recently described by our group to study and characterize the phenomenon of C. albicans biofilm dispersion. Rather than an end-stage process, our results indicate that dispersion occurs at all different stages of the biofilm developmental cycle and is influenced by nutritional and other physiochemical conditions. In addition, our findings provide initial insights into how this process is regulated at the molecular level. We also demonstrate that dispersed cells display distinct phenotypic properties that are associated with increased virulence, with important clinical repercussions.
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影响因子：
3.8
作者：
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通讯作者：
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通讯作者：
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