Sabra Ayman, Biteau Nicolas, Dupuy Jean-William, Klopp Christophe, Noël Thierry, Dementhon Karine
Vaccines Medical Department, Pfizer, 23-25 Av du Dr Lannelongue, F-75014 Paris, France.
Univ. Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, F-33000 Bordeaux, France.
J Fungi (Basel). 2023 Mar 8;9(3):333. doi: 10.3390/jof9030333.
is an emerging opportunistic pathogenic yeast capable of shifting from yeast to pseudohyphae form, and it is one of the few species with the ability to reproduce sexually. In this study, we showed that a Δ mutant, inactivated for a putative pyrophosphatase, is impaired in cell separation, pseudohyphal growth and mating. The defective phenotypes were not restored after the reconstruction of a wild-type locus, reinforcing the hypothesis of the presence of an additional mutation that we suspected in our previous study. Genetic crosses and genome sequencing identified an additional mutation in , encoding a subunit of the mediator complex that functions as a general transcriptional co-activator in Eukaryotes. We confirmed that inactivation of was responsible for the defective phenotypes by rescuing the Δ mutant with a wild-type copy of and constructing a Δ knockout mutant that mimics the phenotypes of Δ in vitro. Proteomic analyses revealed the biological processes under the control of Med15 and involved in hyphal growth, cell separation and mating. This is the first description of the functions of in the regulation of hyphal growth, cell separation and mating, and the pathways involved in .
是一种新兴的机会致病性酵母，能够从酵母形态转变为假菌丝形态，并且是少数具有有性繁殖能力的物种之一。在本研究中，我们发现一个假定的焦磷酸酶失活的Δ突变体在细胞分离、假菌丝生长和交配方面存在缺陷。在野生型基因座重建后，缺陷表型并未恢复，这强化了我们在先前研究中怀疑存在额外突变的假设。遗传杂交和基因组测序确定了基因中的另一个突变，该基因编码中介体复合物的一个亚基，该复合物在真核生物中作为一般转录共激活因子发挥作用。我们通过用野生型拷贝拯救Δ突变体并构建在体外模拟Δ表型的Δ敲除突变体，证实了基因失活是导致缺陷表型的原因。蛋白质组学分析揭示了Med15控制下并参与菌丝生长、细胞分离和交配的生物学过程。这是首次描述基因在调节菌丝生长、细胞分离和交配以及相关途径中的功能。
