Biofilm matrix regulation by Candida albicans Zap1.
Biofilm matrix regulation by Candida albicans Zap1.
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DOI：
10.1371/journal.pbio.1000133
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发表时间：
2009-06
期刊：
影响因子：
9.8
通讯作者：
Mitchell AP
中科院分区：
文献类型：
--
作者：
Nobile CJ;Nett JE;Hernday AD;Homann OR;Deneault JS;Nantel A;Andes DR;Johnson AD;Mitchell AP
锌响应转录因子Zap 1在真菌生物膜形成中具有显著作用，并据报道调节基质形成。生物膜是包埋在细胞外聚合物基质中的微生物的表面相关群体。生物膜是微生物的一种主要自然生长形式，也是普遍器械相关感染的原因。本报告重点介绍了人类主要真菌病原体白色念珠菌的生物膜基质。我们在这里报告说，C。在体外和体内生物膜模型中，白色念珠菌锌应答转录因子Zap 1是主要基质组分可溶性β-1，3葡聚糖的负调节因子。为了了解Zap 1和基质之间的机制关系，我们通过表达谱和全基因组染色质免疫沉淀鉴定了Zap 1靶基因。在这些结果的基础上，我们设计了额外的实验，表明两种葡糖淀粉酶Gca 1和Gca 2在基质生产中具有积极作用，并可能通过水解不溶性β-1，3葡聚糖链发挥作用。我们还表明，一组酒精脱氢酶Adh 5，Csh 1和Ifd 6在基质生产中的作用：Adh 5的积极作用，Csh 1和Ifd 6，负。我们认为这些醇脱氢酶产生群体感应芳基和酰基醇，这些醇反过来又控制生物膜成熟中的多个事件。我们的研究结果定义了一种新型的调节回路及其控制感染核心过程的机制。生物膜是一种表面相关的微生物群体，其嵌入细胞外化合物的水泥中。这种水泥被称为基质。基质的两个主要功能是保护细胞免受周围环境的影响，防止药物和其他压力渗透生物膜，并保持生物膜的结构稳定性，作为胶水将细胞保持在一起。基质的存在是导致在生物膜中观察到的抗微生物药物高度耐药性的一个因素。由于生物膜对人类健康有重大影响，并且由于基质是生物膜的关键组成部分，因此了解基质的产生是如何调节的非常重要。我们已经开始解决这个问题，在主要的人类真菌病原体白色念珠菌。我们发现，锌反应调节蛋白Zap 1控制着几个基因的表达，这些基因对C.白色念珠菌。这些靶基因编码葡糖淀粉酶和醇脱氢酶，这些酶可能控制不同基质成分的合成。这里的发现提供了对有助于生物膜形成的代谢过程的深入了解，并表明Zap 1广泛地作为生物膜成熟的负调节剂发挥作用。
The zinc-responsive transcription factor Zap1 has a striking role in fungal biofilm formation and is reported to regulate matrix formation. A biofilm is a surface-associated population of microorganisms embedded in a matrix of extracellular polymeric substances. Biofilms are a major natural growth form of microorganisms and the cause of pervasive device-associated infection. This report focuses on the biofilm matrix of Candida albicans, the major fungal pathogen of humans. We report here that the C. albicans zinc-response transcription factor Zap1 is a negative regulator of a major matrix component, soluble β-1,3 glucan, in both in vitro and in vivo biofilm models. To understand the mechanistic relationship between Zap1 and matrix, we identified Zap1 target genes through expression profiling and full genome chromatin immunoprecipitation. On the basis of these results, we designed additional experiments showing that two glucoamylases, Gca1 and Gca2, have positive roles in matrix production and may function through hydrolysis of insoluble β-1,3 glucan chains. We also show that a group of alcohol dehydrogenases Adh5, Csh1, and Ifd6 have roles in matrix production: Adh5 acts positively, and Csh1 and Ifd6, negatively. We propose that these alcohol dehydrogenases generate quorum-sensing aryl and acyl alcohols that in turn govern multiple events in biofilm maturation. Our findings define a novel regulatory circuit and its mechanism of control of a process central to infection. A biofilm is a surface-associated population of microbes that is embedded in a cement of extracellular compounds. This cement is known as matrix. The two main functions of matrix are to protect cells from their surrounding environment, preventing drugs and other stresses from penetrating the biofilm, and to maintain the architectural stability of the biofilm, acting as a glue to hold the cells together. The presence of matrix is a contributing factor to the high degree of resistance to antimicrobial drugs observed in biofilms. Because biofilms have a major impact on human health, and because matrix is such a pivotal component of biofilms, it is important to understand how the production of matrix is regulated. We have begun to address this question in the major human fungal pathogen Candida albicans. We found that the zinc-responsive regulatory protein Zap1 controls the expression of several genes important for matrix formation in C. albicans. These target genes encode glucoamylases and alcohol dehydrogenases, enzymes that probably govern the synthesis of distinct matrix constituents. The findings here offer insight into the metabolic processes that contribute to biofilm formation and indicate that Zap1 functions broadly as a negative regulator of biofilm maturation.
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影响因子：
56.9
作者：
Hillenmeyer, Maureen E.;Fung, Eula;Giaever, Guri
通讯作者：
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DOI：
10.1073/pnas.0401416101
发表时间：
2004-04-06
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影响因子：
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