Comparative phenotypic analysis of the major fungal pathogens Candida parapsilosis and Candida albicans.
Comparative phenotypic analysis of the major fungal pathogens Candida parapsilosis and Candida albicans.
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DOI：
10.1371/journal.ppat.1004365
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发表时间：
2014-09
期刊：
影响因子：
6.7
通讯作者：
Butler G
中科院分区：
文献类型：
--
作者：
Holland LM;Schröder MS;Turner SA;Taff H;Andes D;Grózer Z;Gácser A;Ames L;Haynes K;Higgins DG;Butler G
假丝酵母菌和白色假丝酵母菌是酵母菌门中CTG分支的人类真菌病原体。与白色念珠菌相比，人们对傍裂念珠菌的毒力特性知之甚少，傍裂念珠菌是一种与早产儿感染特别相关的病原体。我们在此描述了携带100个转录因子、蛋白激酶和物种特异性基因双等位基因缺失的假丝孢杆菌菌株的构建。每个靶基因构建了两个独立的缺失。测试了bbb40条件下的生长，包括碳源、温度和抗真菌药物的存在。将其表型与同源转录因子缺失的白色念珠菌菌株进行比较。我们发现许多表型在这两个物种之间是共享的，例如Upc2作为唑抗性的调节剂，以及CAP1在氧化应激反应中的作用。另一些则是一个物种所特有的。例如，Cph2在假丝酵母菌的缺氧反应中起作用，而在白色念珠菌中不起作用。我们发现两个物种的生物膜调节因子之间存在广泛的差异。我们鉴定了7个转录因子和1个蛋白激酶，它们是C. parapsilosis生物膜发育所必需的。只有三种（Efg1， Bcr1和Ace2）对白色念珠菌生物膜有类似的作用，而Cph2， Czf1， Gzf3和Ume6仅在假丝酵母菌中起主要作用。两个转录因子（Brg1和Tec1）在白色念珠菌的生物膜形成中有很好的作用，但在假丝念珠菌中却没有相同的功能。我们还比较了假丝胞菌和白色假丝胞菌生物膜的转录谱。我们的分析表明，两个物种之间共享的过程主要是代谢过程，Cph2和Bcr1是C. parapsilosis的主要生物膜调节因子。念珠菌是全世界最常见的真菌感染原因之一。感染既可以是社区感染，也可以是医院获得性感染，尤其与免疫功能低下的个体相关。白色念珠菌是最常见的分离种，也是研究得最好的。然而，其他物种也越来越受到关注。假丝酵母菌病在新生儿病房引起感染暴发，是少数从卫生保健工作者手中转移的假丝酵母菌之一。像白色念珠菌一样，假丝酵母菌以生物膜（细胞群落）的形式生长在留置的医疗器械（如喂食管）表面。我们在这里描述了一套工具的构建，使我们能够表征C. parapsilosis的毒力特性，特别是其作为生物膜生长的能力。我们发现一些调节机制与白色念珠菌共享，但其他的是每个物种独有的。我们的工具，基于选择性地删除调控基因，将为真菌研究界提供一个主要资源。
Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CTG clade in the Saccharomycotina. In contrast to C. albicans, relatively little is known about the virulence properties of C. parapsilosis, a pathogen particularly associated with infections of premature neonates. We describe here the construction of C. parapsilosis strains carrying double allele deletions of 100 transcription factors, protein kinases and species-specific genes. Two independent deletions were constructed for each target gene. Growth in >40 conditions was tested, including carbon source, temperature, and the presence of antifungal drugs. The phenotypes were compared to C. albicans strains with deletions of orthologous transcription factors. We found that many phenotypes are shared between the two species, such as the role of Upc2 as a regulator of azole resistance, and of CAP1 in the oxidative stress response. Others are unique to one species. For example, Cph2 plays a role in the hypoxic response in C. parapsilosis but not in C. albicans. We found extensive divergence between the biofilm regulators of the two species. We identified seven transcription factors and one protein kinase that are required for biofilm development in C. parapsilosis. Only three (Efg1, Bcr1 and Ace2) have similar effects on C. albicans biofilms, whereas Cph2, Czf1, Gzf3 and Ume6 have major roles in C. parapsilosis only. Two transcription factors (Brg1 and Tec1) with well-characterized roles in biofilm formation in C. albicans do not have the same function in C. parapsilosis. We also compared the transcription profile of C. parapsilosis and C. albicans biofilms. Our analysis suggests the processes shared between the two species are predominantly metabolic, and that Cph2 and Bcr1 are major biofilm regulators in C. parapsilosis. Candida species are among the most common causes of fungal infection worldwide. Infections can be both community-based and hospital-acquired, and are particularly associated with immunocompromised individuals. Candida albicans is the most commonly isolated species and is the best studied. However, other species are becoming of increasing concern. Candida parapsilosis causes outbreaks of infection in neonatal wards, and is one of the few Candida species that is transferred from the hands of healthcare workers. C. parapsilosis, like C. albicans, grows as biofilms (cell communities) on the surfaces of indwelling medical devices like feeding tubes. We describe here the construction of a set of tools that allow us to characterize the virulence properties of C. parapsilosis, and in particular its ability to grow as biofilms. We find that some of the regulatory mechanisms are shared with C. albicans, but others are unique to each species. Our tools, based on selectively deleting regulatory genes, will provide a major resource to the fungal research community.
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影响因子：
30.3
作者：
Chen C;Pande K;French SD;Tuch BB;Noble SM
通讯作者：
Noble SM
Bcr1 和 CFEM 蛋白在近平滑念珠菌和白色念珠菌中的保守和不同作用。
影响因子：
3.7
作者：
Ding C;Vidanes GM;Maguire SL;Guida A;Synnott JM;Andes DR;Butler G
通讯作者：
Butler G
影响因子：
--
作者：
Baek, Yong-Un;Li, Mingchun;Davis, Dana A.
通讯作者：
Davis, Dana A.
影响因子：
9.4
作者：
Clark, TA;Slavinski, SA;Hajjeh, RA
通讯作者：
Hajjeh, RA
影响因子：
10.5
作者：
DOHRMANN, PR;BUTLER, G;STILLMAN, DJ
通讯作者：
STILLMAN, DJ