Meza-Davalos Teresa, García-Ortega Luis F, Mancera Eugenio
Departamento de Ingeniería Genética, Unidad Irapuato, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Irapuato, Mexico.
Mol Microbiol. 2025 Jul 17. doi: 10.1111/mmi.70012.
Candida dubliniensis is the most closely related species to C. albicans, one of the leading causes of fungal infections in humans. However, despite sharing many characteristics, C. dubliniensis is significantly less pathogenic. To better understand the molecular underpinnings of these dissimilarities, we focused on the regulation of filamentation, a developmental trait fundamental for host colonization. We generated a collection of 44 C. dubliniensis null mutants of transcription regulators whose orthologs in C. albicans had been previously implicated in filamentous growth. These regulators are very similar at the sequence level, but phenotypic screening identified several mutants with contrasting interspecific filamentation phenotypes beyond previously known differences. Bcr1, a well-known regulator of biofilm formation, stands out as its mutant mainly showed a filamentation defect in C. dubliniensis. Phenotypic and transcriptional characterization showed that the bcr1 defect is condition dependent and that this regulator plays a central role in the filamentation of C. dubliniensis, possibly by regulating the hyphal activator Ume6. Overall, our results suggest that several regulatory pathways are involved in the filamentation differences between C. albicans and C. dubliniensis and show that the C. dubliniensis mutant collection is a valuable resource to compare, at a molecular level, these species of medical relevance.
都柏林念珠菌是与白色念珠菌关系最为密切的物种，白色念珠菌是人类真菌感染的主要病因之一。然而，尽管都柏林念珠菌与白色念珠菌有许多共同特征，但其致病性却显著较低。为了更好地理解这些差异的分子基础，我们聚焦于丝状化的调控，丝状化是宿主定殖所必需的一种发育特性。我们构建了一个包含44个都柏林念珠菌转录调节因子缺失突变体的文库，这些调节因子在白色念珠菌中的直系同源物先前已被证明与丝状生长有关。这些调节因子在序列水平上非常相似，但表型筛选发现了几个突变体，它们具有种间丝状化表型差异，这些差异超出了先前已知的范围。Bcr1是一种众所周知的生物膜形成调节因子，其突变体在都柏林念珠菌中主要表现出丝状化缺陷。表型和转录特征表明，bcr1缺陷是条件依赖性的，并且该调节因子在都柏林念珠菌的丝状化过程中起着核心作用，可能是通过调节菌丝激活因子Ume6来实现的。总体而言，我们的结果表明，几种调控途径参与了白色念珠菌和都柏林念珠菌之间的丝状化差异，并且表明都柏林念珠菌突变体文库是在分子水平上比较这些具有医学相关性的物种的宝贵资源。
