Conserved Autophagy Pathway Contributes to Stress Tolerance and Virulence and Differentially Controls Autophagic Flux Upon Nutrient Starvation in Cryptococcus neoformans
Conserved Autophagy Pathway Contributes to Stress Tolerance and Virulence and Differentially Controls Autophagic Flux Upon Nutrient Starvation in Cryptococcus neoformans
复制标题
保守的自噬途径有助于新型隐球菌的应激耐受性和毒力，并在营养饥饿时差异性地控制自噬通量
DOI：
10.3389/fmicb.2019.02690
复制
发表时间：
2019-11-26
影响因子：
5.2
通讯作者：
Wei, Dongsheng
中科院分区：
文献类型：
--
作者：
Zhao, Xueru;Feng, Weijia;Wei, Dongsheng
自噬主要是一种分解代谢过程，用于科普营养缺乏和各种胁迫条件。新生隐球菌是免疫功能低下个体的主要病原真菌，在人类环境中常受到各种应激，因此，新生隐球菌的自噬反应与其自身的免疫功能密切相关。这些压力往往决定了它在宿主中的生存。然而，关于自噬相关基因（ATG）如何影响自噬流量、毒力、应激反应和致病性的系统研究尚不多见。新生儿缺乏。本研究构建了22株ATG缺陷型菌株，探讨了其在致病性、胁迫反应、耐饥饿性和自噬通量等方面的作用。新人类结果表明，Atg 6和Atg 14 -03对C. neoformans在37°C和漆酶的生产。此外，atg 2 Δ和atg 6 Δ菌株对过氧化氢引起的氧化应激敏感。在Galleria mellonella模型中，约有一半的atgΔ菌株对1.5M NaCl的敏感性高于野生型，而毒力则明显低于野生型。C.自噬流新生儿依赖于Atg 1-Atg 13、Atg 5-Atg 12-Atg 16和Atg 2-Atg 18复合物和Atg 11。在这些自噬缺陷突变体中难以检测到来自Atg 8的绿色荧光蛋白（GFP）的切割;然而，在atg 3 Δ、atg 4 Δ、atg 6 Δ和atg 14 Δ菌株中检测到。此外，在C.新人类我们的研究结果表明，这些ATG基因有助于差异的碳和氮饥饿耐受性在C。neoformans与S.啤酒。总的来说，这项研究推进了我们对ATG基因在C.新人类
Autophagy is mainly a catabolic process, which is used to cope with nutrient deficiency and various stress conditions. Human environment often imposes various stresses on Cryptococcus neoformans, a major fungal pathogen of immunocompromised individuals; therefore, autophagic response of C. neoformans to these stresses often determines its survival in the host. However, a systematic study on how autophagy related (ATG) genes influence on autophagic flux, virulence, stress response and pathogenicity of C. neoformans is lacking. In this study, 22 ATG-deficient strains were constructed to investigate their roles in virulence, pathogenesis, stress response, starvation tolerance and autophagic flux in C. neoformans. Our results showed that Atg6 and Atg14-03 significantly affect the growth of C. neoformans at 37°C and laccase production. Additionally, atg2Δ and atg6Δ strains were sensitive to oxidative stress caused by hydrogen peroxide. Approximately half of the atgΔ strains displayed higher sensitivity to 1.5 M NaCl and remarkably lower virulence in the Galleria mellonella model than the wild type. Autophagic flux in C. neoformans was dependent on the Atg1-Atg13, Atg5-Atg12-Atg16, and Atg2-Atg18 complexes and Atg11. Cleavage of the green fluorescent protein (GFP) from Atg8 was difficult to detect in these autophagy defective mutants; however, it was detected in the atg3Δ, atg4Δ, atg6Δ and atg14Δ strains. Additionally, no homologs of Saccharomyces cerevisiae ATG10 were detected in C. neoformans. Our results indicate that these ATG genes contribute differentially to carbon and nitrogen starvation tolerance in C. neoformans compared with S. cerevisiae. Overall, this study advances our knowledge of the specific roles of ATG genes in C. neoformans.