Post-translational changes in Phialophora verrucosa via lysine lactylation during prolonged presence in a patient with a CARD9-related immune disorder.
Post-translational changes in Phialophora verrucosa via lysine lactylation during prolonged presence in a patient with a CARD9-related immune disorder.
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疣状瓶霉在长期存在于患有 CARD9 相关免疫疾病的患者体内时，通过赖氨酸乳酰化而发生翻译后变化
DOI：
10.3389/fimmu.2022.966457
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
CARD 9相关的遗传性免疫疾病是慢性播散性真菌感染的主要危险因素。除了念珠菌和皮肤真菌的病原体，黑酵母样真菌的环境机会在该患者队列中相对频繁。尤其是瓶霉属的数量过多。我们调查了两个分离株的一个菌株疣状假单胞菌居住在CARD 9患者，采样间隔十年。基因组，黑化和抗真菌敏感性的祖先和衍生菌株进行了比较，和潜在的适应宿主栖息地进行了研究与蛋白质组学技术使用翻译后修饰作为代理。使用高准确度nano-LC-MS/MS结合从消化的细胞裂解物中富集乳酸化肽和随后的肽鉴定进行全局乳酸化分析。该分离株基因组中积累了6945个SNPs，其中31个在CDS中检测到。大量鉴定的蛋白质被显著富集，例如在黑色素生物合成中。在420个蛋白质上共检测到636个乳糖化位点，包含26种修饰基序。在核糖体的23个组成蛋白中发现赖氨酸乳酸化（Kla），表明Kla在蛋白质合成中的影响。12个乳酸化蛋白参与致病作用。蛋白质-蛋白质相互作用（PPI）网络分析表明，蛋白质乳酸化广泛分布，影响各种生物过程。我们的研究结果揭示了赖氨酸乳酸化在调节黑真菌代谢和黑色素生物合成中的广泛作用。在基因组中观察到几个大的重排和倒位，但基因组的变化不能与适应或已知的临床相关特性的祖衍生分离物，在体外抗真菌药敏性基本上保持不变。
CARD9-related inherited immune disorders are a major risk factor for chronic disseminated fungal infection. In addition to pathogens of Candida and dermatophytes, the environmental opportunists of the black yeast-like fungi are relatively frequent in this patient cohort. Particularly the genus Phialophora is overrepresented. We investigated two isolates of a strain of P. verrucosa residing in a CARD9 patient, sampled with a period of ten years apart. Genomes, melanization and antifungal susceptibility of progenitor and derived strains were compared, and potential adaptation to the host habitat was investigated with proteomic techniques using post-translational modification as a proxy. Global lactylation analysis was performed using high accuracy nano-LC-MS/MS in combination with enrichment of lactylated peptides from digested cell lysates, and subsequent peptide identification. The genome of the derived isolate had accumulated 6945 SNPs, of which 31 were detected in CDS. A large number of identified proteins were significantly enriched, e.g. in melanin biosynthesis. A total of 636 lactylation sites on 420 lactylated proteins were identified, which contained in 26 types of modification motifs. Lysine lactylation (Kla) was found in 23 constituent proteins of the ribosome, indicating an impact of Kla in protein synthesis. Twelve lactylated proteins participated in pathogenicity. A protein-protein interaction (PPI) network analysis suggested that protein lactylations are widely distributed influencing various biological processes. Our findings reveal widespread roles for lysine lactylation in regulating metabolism and melanin biosynthesis in black fungi. Several large rearrangements and inversions were observed in the genome, but genomic changes could not be linked to adaptation or to known clinically relevant properties of progenitor to derived isolate; in vitro antifungal susceptibility had largely remained unaltered.
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影响因子：
5.2
作者：
Guillamón JM;Barrio E
通讯作者：
Barrio E
DOI：
10.3390/jof7090723
发表时间：
2021-09-04
期刊：
Journal of fungi (Basel, Switzerland)
影响因子：
--
作者：
Gostinčar C;Stajich JE;Kejžar A;Sinha S;Nislow C;Lenassi M;Gunde-Cimerman N
通讯作者：
Gunde-Cimerman N
影响因子：
5.5
作者：
Bonifaz, Alexandro;Davoudi, Mehrnaz Mohammad;Badali, Hamid
通讯作者：
Badali, Hamid
影响因子：
7
作者：
Li, Ruiqiang;Zhu, Hongmei;Wang, Jun
通讯作者：
Wang, Jun
影响因子：
5.8
作者：
Cheng, Alice;Grant, Charles E.;Bailey, Timothy L.
通讯作者：
Bailey, Timothy L.