Gluconate Kinase Is Required for Gluconate Assimilation and Sporulation in Cryptococcus neoformans.
Gluconate Kinase Is Required for Gluconate Assimilation and Sporulation in Cryptococcus neoformans.
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DOI：
10.1128/spectrum.00301-22
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发表时间：
2022-04-27
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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新型隐球菌是一种环境酵母菌，也是一种机会致病菌。致病的能力取决于适应人类宿主的能力。先前的研究涉及感染相关激酶3（IRK 3，CNAG_03048），这是建立感染所需的。我们在遗传学和生物化学上将IRK 3表征为葡萄糖酸激酶，并建议命名为GNK 1。这种代谢酶利用葡萄糖酸盐产生6-磷酸葡萄糖酸盐，作为戊糖磷酸途径（AOXPPP）的替代氧化相的一部分。GNK 1的存在证实了AOXPPP的存在，并能够弥补传统OXPPP的损失，为它的非本质性提供了解释。C.新生儿可以以依赖GNK 1的方式利用葡萄糖酸盐作为替代碳源。在我们努力了解GNK 1在宿主适应和毒力中的作用时，我们发现GNK 1缺陷突变体在多个菌株中具有可变的毒力和二氧化碳耐受性，这表明第二位点突变经常与GNK 1缺失突变相互作用。在我们通过回交实验分离这些遗传位点的努力中，我们发现GNK 1缺陷菌株不能形成孢子。这些数据表明，葡萄糖酸代谢是至关重要的孢子形成的C。新人类新生隐球菌是一种真菌病原体，每年导致近18万人死亡。我们鉴定了一个名为GNK 1的基因，该基因似乎与其他与C.作为病原体。虽然这些相互作用的遗传位点仍然难以捉摸，但我们发现GNK 1在代谢和交配/孢子形成中起作用。对GNK 1在有性生殖中的机制作用的进一步研究可能会发现一个更大的基因网络，这些基因对宿主适应和毒力很重要。
Cryptococcus neoformans is an environmental yeast and an opportunistic human pathogen. The ability to cause disease depends on the ability to adapt to the human host. Previous studies implicated infectivity-related kinase 3 (IRK3, CNAG_03048) as required for establishing an infection. We genetically and biochemically characterized IRK3 as a gluconate kinase and propose the name GNK1. This metabolic enzyme utilizes gluconate to produce 6-phosphogluconate as part of the alternative oxidative phase of the pentose phosphate pathway (AOXPPP). The presence of GNK1 confirms that the AOXPPP is present and able to compensate for loss of the traditional OXPPP, providing an explanation for its nonessentiality. C. neoformans can utilize gluconate as an alternative carbon source in a GNK1-dependent manner. In our efforts to understand the role of GNK1 in host adaptation and virulence, we found that GNK1-deficient mutants have variable virulence and carbon dioxide tolerance across multiple strains, suggesting that second site mutations frequently interact with GNK1 deletion mutations. In our effort to isolate these genetic loci by backcrossing experiments, we discovered that GNK1-deficient strains are unable to sporulate. These data suggest that gluconate metabolism is critical for sporulation of C. neoformans. IMPORTANCE Cryptococcus neoformans is a fungal pathogen that contributes to nearly 180,000 deaths annually. We characterized a gene named GNK1 that appears to interact with other genetic loci involved with the ability of C. neoformans to act as a pathogen. While these interacting genetic loci remain elusive, we discovered that GNK1 plays roles in both metabolism and mating/sporulation. Further interrogation of the mechanistic role for GNK1 in sexual reproduction may uncover a larger network of genes that are important for host adaptation and virulence.
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影响因子：
--
作者：
Stincone A;Prigione A;Cramer T;Wamelink MM;Campbell K;Cheung E;Olin-Sandoval V;Grüning NM;Krüger A;Tauqeer Alam M;Keller MA;Breitenbach M;Brindle KM;Rabinowitz JD;Ralser M
通讯作者：
Ralser M
隐球菌病诊断和治疗：我们现在知道什么。
影响因子：
3
作者：
Perfect, John R.;Bicanic, Tihana
通讯作者：
Bicanic, Tihana
影响因子：
3.1
作者：
Sweeney, NJ;Laux, DC;Cohen, PS
通讯作者：
Cohen, PS
DOI：
10.1073/pnas.1215283110
发表时间：
2013-06-11
影响因子：
11.1
作者：
Flamholz, Avi;Noor, Elad;Milo, Ron
通讯作者：
Milo, Ron
影响因子：
3
作者：
Fan, Cheng-Li;Han, Lian-Tao;Liu, Tong-Bao
通讯作者：
Liu, Tong-Bao