Candida albicans biofilm dispersion as a key step during candidiasis

描述（由申请人提供）：念珠菌病现在是美国和世界范围内医院中第三大最常见的医院感染，而C。白色念珠菌仍然是念珠菌病最常见的病原体。不幸的是，这些感染的死亡率高得令人无法接受。绦虫病通常与生物膜形成有关，一旦建立，生物膜有可能通过提供安全的避难所来启动或延长感染，生物体可以从该避难所侵入局部组织，播种新的感染部位并抵抗根除努力。生物膜积累是附着、生长和分散过程平衡的结果。毫无疑问，在这些现象中，最不了解的是生物膜分散。在C.白色念珠菌这是特别令人担忧的，因为生物膜分散是代表与易感患者中威胁生命的临床感染相关的主要罪魁祸首的步骤：正是分离的细胞负责败血症和在侵袭性疾病建立之前传播到靶器官。重要的是，这两种临床表现（念珠菌血症和全身侵袭性念珠菌病）与高发病率和死亡率相关。因此，拟议的研究的主要目标是检查生物膜分散的过程。为此，我们将：i）识别与C相关的环境信号。白念珠菌生物膜分散，ii）鉴定生物膜分散中涉及的分子机制，和iii）分析从生物膜分散的酵母细胞的表型，特别强调粘附特性、耐药性和毒力。拟议的研究是创新的，因为它研究生物膜，现代微生物学的主要范式之一。此外，它集中在一个过程，生物膜分散，这在很大程度上被忽视，在过去的C。白色念珠菌研究人员。公共卫生相关性：生物膜的形成对人类健康有严重的后果。这项研究背后的主要思想是，我们需要更好地了解C。白色念珠菌细胞从生物膜上脱落或分离，因为这些细胞负责随后在不同器官中建立感染。如果我们阻止这一关键步骤，可能会导致发病率、死亡率和住院时间的大幅降低，同时降低医疗成本。

DESCRIPTION (provided by applicant): Candidiasis now represents the third most frequent nosocomial infection in hospitals both in the US and worldwide, and C. albicans remains the most frequent causative agent of candidiasis. Unfortunately these infections carry unacceptably high mortality rates. Candidiasis is often associated with biofilm formation and once established, biofilms have the potential to initiate or prolong infections by providing a safe sanctuary from which organisms can invade local tissue, seed new infection sites and resist eradication efforts. Biofilm accumulation results from the balance of attachment, growth, and dispersion processes. Without any question, of these phenomena, the least understood is biofilm dispersion. In the case of C. albicans this is particularly worrisome because biofilm dispersion is the step that represents the main culprit associated with life-threatening clinical infections in susceptible patients: it is precisely the detached cells that are responsible for septicemia and for dissemination to target organs prior to the establishment of invasive disease. Importantly, both of these clinical manifestations (candidemia and systemic invasive candidiasis) are associated with the high morbidity and mortality rates. Therefore, the main objective of the proposed studies is to examine the process of biofilm dispersion. To this end we will: i) identify the environmental signals associated with C. albicans biofilm dispersion, ii) identify the molecular mechanisms involved in biofilm dispersion and iii) analyze the phenotypes of yeast cells dispersed from the biofilm, with special emphasis on adhesive properties, drug resistance and virulence. The proposed research is innovative since it studies biofilms, one of the major paradigms of modern microbiology. Moreover, it focuses on a process, biofilm dispersion, that has largely been ignored in the past by C. albicans investigators. PUBLIC HEALTH RELEVANCE: Biofilm formation has severe consequences for human health. The main idea behind this study is that we need to better understand how C. albicans cells detach or separate from biofilms, since these cells are responsible for the subsequent establishment of infections in different organs. If we prevent this critical step, it may lead to a substantial reduction in morbidity, mortality and extended hospital stay, while simultaneously reducing healthcare costs.