Fungal and host protein persulfidation are functionally correlated and modulate both virulence and antifungal response.
Fungal and host protein persulfidation are functionally correlated and modulate both virulence and antifungal response.
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DOI：
10.1371/journal.pbio.3001247
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发表时间：
2021-06
期刊：
影响因子：
9.8
通讯作者：
Amich J
中科院分区：
文献类型：
--
作者：
Sueiro-Olivares M;Scott J;Gago S;Petrovic D;Kouroussis E;Zivanovic J;Yu Y;Strobel M;Cunha C;Thomson D;Fortune-Grant R;Thusek S;Bowyer P;Beilhack A;Carvalho A;Bignell E;Filipovic MR;Amich J
烟曲霉菌是一种人类真菌病原体，可在患有免疫失衡或潜在肺部疾病的个体中引起毁灭性的肺部感染，称为“曲霉菌”。由于快速适应压力是至关重要的宿主-病原体相互作用的结果，在这里，我们研究了多功能翻译后修饰（PTM）过硫化真菌毒力和抗真菌宿主防御的作用。我们证明了一个A.具有低过硫化水平的烟曲霉突变体对宿主介导的杀伤更敏感，并且在鼠感染模型中显示出降低的毒力。此外，我们发现，编码胱硫醚γ-裂解酶（CTH）的人类基因中的单核苷酸多态性（SNP）导致细胞过硫化减少，并与造血干细胞移植受者对侵袭性肺曲霉病（IPA）的易感性相关，因为正确的过硫化水平是受者肺部宿主细胞最佳抗真菌活性所必需的。重要的是，宿主过硫化水平决定真菌过硫化水平，最终反映了宿主-病原体功能相关性，并突出了治疗曲霉病的潜在新治疗靶点。本研究表明，翻译后修饰过硫化作用对真菌毒力和宿主抗真菌反应都很重要。宿主中的过硫化水平与其抗真菌效力相关，影响真菌抵抗宿主攻击所需的水平，反映了功能相关性。因此，调节过硫化可能是一个有前途的策略，以针对病原体和免疫反应。
Aspergillus fumigatus is a human fungal pathogen that can cause devastating pulmonary infections, termed “aspergilloses,” in individuals suffering immune imbalances or underlying lung conditions. As rapid adaptation to stress is crucial for the outcome of the host–pathogen interplay, here we investigated the role of the versatile posttranslational modification (PTM) persulfidation for both fungal virulence and antifungal host defense. We show that an A. fumigatus mutant with low persulfidation levels is more susceptible to host-mediated killing and displays reduced virulence in murine models of infection. Additionally, we found that a single nucleotide polymorphism (SNP) in the human gene encoding cystathionine γ-lyase (CTH) causes a reduction in cellular persulfidation and correlates with a predisposition of hematopoietic stem cell transplant recipients to invasive pulmonary aspergillosis (IPA), as correct levels of persulfidation are required for optimal antifungal activity of recipients’ lung resident host cells. Importantly, the levels of host persulfidation determine the levels of fungal persulfidation, ultimately reflecting a host–pathogen functional correlation and highlighting a potential new therapeutic target for the treatment of aspergillosis. This study reveals that the post-translational modification persulfidation is important for both fungal virulence and the host antifungal response. The level of persulfidation in the host, which correlates with its antifungal potency, impacts the level required in the fungus to counteract host attack, reflecting a functional correlation. Thus modulating persulfidation may be a promising strategy to target both pathogens and immune responses.
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影响因子：
4.8
作者：
Chiku, Taurai;Padovani, Dominique;Banerjee, Ruma
通讯作者：
Banerjee, Ruma
影响因子：
3
作者：
Candida Monteiro, M.;Ramon De Lucas, J.
通讯作者：
Ramon De Lucas, J.
影响因子：
16.6
作者：
Andrianaki AM;Kyrmizi I;Thanopoulou K;Baldin C;Drakos E;Soliman SSM;Shetty AC;McCracken C;Akoumianaki T;Stylianou K;Ioannou P;Pontikoglou C;Papadaki HA;Tzardi M;Belle V;Etienne E;Beauvais A;Samonis G;Kontoyiannis DP;Andreakos E;Bruno VM;Ibrahim AS;Chamilos G
通讯作者：
Chamilos G
DOI：
10.3390/jof3040057
发表时间：
2017-10-18
期刊：
Journal of fungi (Basel, Switzerland)
影响因子：
--
作者：
Bongomin F;Gago S;Oladele RO;Denning DW
通讯作者：
Denning DW
影响因子：
3.1
作者：
Amich, Jorge;Duemig, Michaela;Krappmann, Sven
通讯作者：
Krappmann, Sven