Sulphiredoxin plays peroxiredoxin-dependent and -independent roles via the HOG signalling pathway in Cryptococcus neoformans and contributes to fungal virulence.
Sulphiredoxin plays peroxiredoxin-dependent and -independent roles via the HOG signalling pathway in Cryptococcus neoformans and contributes to fungal virulence.
复制标题
DOI：
10.1111/mmi.12388
复制
发表时间：
2013-11
影响因子：
3.6
通讯作者：
Bahn YS
中科院分区：
文献类型：
--
作者：
Upadhya R;Kim H;Jung KW;Park G;Lam W;Lodge JK;Bahn YS
氧化应激抵抗机制是真菌病原体在人体内存活和增殖的关键毒力因子。在这项研究中，我们鉴定了硫氧还蛋白Srx1在引起真菌性脑膜脑炎的新生隐球菌的氧化应激抵抗中的作用，以及对过氧化还蛋白Tsa1和Tsa3以及硫氧还蛋白Trx1和Trx2的调节。新生芽孢杆菌HOG(High Osmolality Glycerol，高渗透压甘油)途径在过氧化胁迫条件下SRX1的转录调控中起着至关重要的作用。一项基因缺失研究表明，细胞需要Srx1来对抗过氧化应激，但不需要其他氧化损伤剂。HOG1被发现在诱导对过氧化应激的适应性反应的同时以SRX1非依赖的方式抑制麦角固醇的生物合成是必不可少的。与此一致的是，低剂量和高剂量的外源过氧化氢处理都调节了新生梭菌Hog1的磷酸化。用新生弧菌Tsa1特异性抗体进行的免疫印迹分析表明，Srx1和Trx1对于氧化的Tsa1的循环是必不可少的。除了在过氧化物感应中的作用外，新生隐孢子菌的srx1也被发现在促进杀菌剂依赖的细胞肿胀和生长停滞中具有不依赖于过氧化还蛋白的功能。最后，我们通过一个小鼠感染模型证明了新生隐孢子菌Srx1在真菌致病中的重要性，证明了它需要完全毒力。
Mechanisms of oxidative stress resistance are crucial virulence factors for survival and proliferation of fungal pathogens within the human host. In this study we have identified and functionally characterized the role of sulfiredoxin, Srx1, in oxidative stress resistance of Cryptococcus neoformans causing fungal meningoencephalitis and regulation of peroxiredoxins, Tsa1 and Tsa3, and thioredoxins, Trx1 and Trx2. The C. neoformans HOG (High Osmolarity Glycerol) pathway was essential for the transcriptional regulation of SRX1 under peroxide stress conditions. A gene deletion study revealed that Srx1 was required for cells to counteract peroxide stress, but not other oxidative damaging agents. HOG1 was found to be essential for the induction of adaptive response to peroxide stress with concurrent repression of ergosterol biosynthesis in an SRX1-independent manner. Consistent with this, phosphorylation of C. neoformans Hog1 was modulated by both low and high doses of exogenous hydrogen peroxide treatment. Immunoblot analysis using the C. neoformans Tsa1 specific antibody revealed that both Srx1 and Trx1 were essential for recycling of oxidized Tsa1. In addition to its role in peroxide sensing and response C. neoformans Srx1 was also found to be required for a peroxiredoxin-independent function in promoting fungicide-dependent cell swelling and growth arrest. Finally we showed the importance of C. neoformans Srx1 in fungal pathogenesis by demonstrating its requirement for full virulence using a mouse infection model.
登录
查看更多内容
影响因子：
5.5
作者：
Brummer, E
通讯作者：
Brummer, E
影响因子：
3.3
作者：
Bahn, YS;Kojima, K;Heitman, J
通讯作者：
Heitman, J
影响因子：
11.2
作者：
Findlay, Victoria J.;Townsend, Danyelle M.;Tew, Kenneth D.
通讯作者：
Tew, Kenneth D.
影响因子：
10.5
作者：
KAMADA, Y;JUNG, US;LEVIN, DE
通讯作者：
LEVIN, DE
影响因子：
16
作者：
Day, Alison M.;Brown, Jonathon D.;Veal, Elizabeth A.
通讯作者：
Veal, Elizabeth A.