The role of the C. albicans transcriptional repressor NRG1 during filamentation and disseminated candidiasis is strain-dependent.
The role of the C. albicans transcriptional repressor NRG1 during filamentation and disseminated candidiasis is strain-dependent.
复制标题
白色念珠菌转录抑制因子 NRG1 在丝状形成和播散性念珠菌病期间的作用是菌株依赖性的。
DOI：
10.1101/2023.12.15.571891
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Krysan,DamianJ
中科院分区：
文献类型：
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作者：
Wakade,RohanS;Wellington,Melanie;Krysan,DamianJ
白色念珠菌是人类浅表性和侵袭性真菌疾病最常见的原因之一。它引起疾病的能力与它经历从芽殖酵母到丝状形式（菌丝和假菌丝）的形态转变的能力密切相关。C的程度。从患者分离的白念珠菌菌株发生了显著变化。此外，涉及正向调节菌丝形态发生的转录因子的突变体的表达表型也可以因菌株而异。在此，我们对四种致病力差的C.白念珠菌及其相应的丝状体NRG 1阻遏物缺失突变体。两个最强毒力的菌株，57055和78048，表现出robustin vivoenergization，但主要是在体外菌丝诱导酵母相;两个低毒力菌株（94015和78042）不进行energization以及在任何condition.In体外，删除NRG 1增加菌丝形成的SC 5314衍生物SN 250，但只有假菌丝形成的临床分离物。NRG 1的缺失适度地增加了78042的毒力，这伴随着菌丝相关基因的表达增加而没有增加表达。值得注意的是，78048中NRG 1的缺失降低了体内丝状菌的形成、念珠菌溶素（ECE 1）的表达和毒力，而没有显著改变感染的建立。因此，保守阻遏蛋白NRG 1 inC.重要的是，人类真菌病原体白色念珠菌的临床分离株在其进行玻璃体化的能力和良好表征的转录调节因子的功能方面表现出显着的差异。在这里，我们表明，Nrg 1，一个关键的阻遏物的deletentation和丝特异性基因表达的标准参考菌株，具有应变依赖性功能，特别是在感染。最引人注目的是，NRG 1功能的丧失可以降低某些菌株的致病性、菌丝特异性基因表达（如毒素念珠菌溶素）和毒力。我们的数据强调，看似基本的和保守的转录调节因子，如Nrg 1的功能是上下文相对于环境和遗传背景。
Candida albicansis one of the most common causes of superficial and invasive fungal diseases in humans. Its ability to cause disease is closely linked to its ability to undergo a morphological transition from budding yeast to filamentous forms (hyphae and pseudohyphae). The extent to whichC. albicansstrains isolated from patients undergo filamentation varies significantly. In addition, the filamentation phenotypes of mutants involving transcription factors that positively regulate hyphal morphogenesis can also vary from strain to strain. Here, we characterized the virulence,in vitroandin vivofilamentation, andin vitroandin vivohypha-associated gene expression profiles for four poorly filamentingC. albicansisolates and their corresponding deletion mutants of the repressor of filamentationNRG1. The two most virulent strains, 57055 and 78048, show robustin vivofilamentation but are predominately yeast phase underin vitrohypha induction; the two low-virulence strains (94015 and 78042) do not undergo filamentation well under either condition.In vitro, deletion ofNRG1increases hyphae formation in the SC5314 derivative SN250, but only pseudohyphae are formed in the clinical isolates. Deletion ofNRG1modestly increased the virulence of 78042, which was accompanied by increased expression of hypha-associated genes without an increase in filamentation. Strikingly, deletion ofNRG1in 78048 reduced filamentationin vivo, expression of candidalysin (ECE1), and virulence without dramatically altering establishment of infection. Thus, the function of the conserved repressorNRG1inC. albicansshows strain-based heterogeneity during infection.IMPORTANCEClinical isolates of the human fungal pathogenCandida albicansshow significant variation in their ability to undergoin vitrofilamentation and in the function of well-characterized transcriptional regulators of filamentation. Here, we show that Nrg1, a key repressor of filamentation and filament specific gene expression in standard reference strains, has strain-dependent functions, particularly during infection. Most strikingly, loss ofNRG1function can reduce filamentation, hypha-specific gene expression such as the toxin candidalysin, and virulence in some strains. Our data emphasize that the functions of seemingly fundamental and well-conserved transcriptional regulators such as Nrg1 are contextual with respect to both environment and genetic backgrounds.