Fungal acetylome comparative analysis identifies an essential role of acetylation in human fungal pathogen virulence.
Yanjian LiHailong LiMingfei SuiMinghui LiJiamei WangYang MengTianshu SunQiaojing LiangChenhao SuoXindi GaoChao LiZhuoran LiWei DuBaihua ZhangSixiang SaiZhang ZhangJing YeHongchen WangShang YueJun-Fang TengManli ZhongChangbin ChenShouliang QiLing LuDancheng LiChen DingPublished in: Communications biology (2019)
Lysine acetylation is critical in regulating important biological processes in many organisms, yet little is known about acetylome evolution and its contribution to phenotypic diversity. Here, we compare the acetylomes of baker's yeast and the three deadliest human fungal pathogens, Cryptococcus neoformans, Candida albicans, and Aspergillus fumigatus. Using mass spectrometry enriched for acetylated peptides together with public data from Saccharomyces cerevisiae, we show that fungal acetylomes are characterized by dramatic evolutionary dynamics and limited conservation in core biological processes. Notably, the levels of protein acetylation in pathogenic fungi correlate with their pathogenicity. Using gene knockouts and pathogenicity assays in mice, we identify deacetylases with critical roles in virulence and protein translation elongation. Finally, through mutational analysis of deactylation motifs we find evidence of positive selection at specific acetylation motifs in fungal pathogens. These results shed new light on the pathogenicity regulation mechanisms underlying the evolution of fungal acetylomes.
Keyphrases
- biofilm formation
- candida albicans
- saccharomyces cerevisiae
- cell wall
- mass spectrometry
- endothelial cells
- pseudomonas aeruginosa
- escherichia coli
- genome wide
- staphylococcus aureus
- antimicrobial resistance
- histone deacetylase
- healthcare
- amino acid
- gram negative
- mental health
- induced pluripotent stem cells
- metabolic syndrome
- machine learning
- pluripotent stem cells
- cystic fibrosis
- liquid chromatography
- high resolution
- high throughput
- insulin resistance
- adipose tissue
- small molecule
- high fat diet induced
- data analysis
- single cell
- copy number