Proteomics

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Post-translational changes in Phialophora verrucosa via lysine lactylation during prolonged presence in a patient with a CARD9-related immune disorder


ABSTRACT: Lysine lactylation (Kla) is a newly discovered histone post-translational modification (PTM), playing important roles in regulating transcription in macrophages. Increasing evidence demonstrates that lysine lactylation plays an important regulatory role in metabolic processes in both bacterial and human cells. However, little is known about the extent and function of lysine lactylation in fungi, here investigated with the black yeast Phialophora verrucosaverrucose as a model organism. WeHere, we report the first proteomic survey of this modification in P. verrucosa. We performed a global lactylation analysis of P. verrucosa using high accuracy bottom-up nano-LC-MS/MS in combination wwith the enrichment of lactylated peptides from digested cell lysates and subsequent peptide identification. In total, 636 lactylation sites on 420 lactylated proteins were identified in this pathogen, of which contained in 26 types of modification motifs. Our results show that over 85% of lactylated proteins were distributed in cytoplasm, mitochondria, and nucleus. The identified proteins were found to be involved associated toin diverse biological processes and were significantly enriched in the melanin biosynthesis process. Most strikingly, Kla was found in 23 structural constituent proteins of ribosome, indicating an impact of Kla in protein synthesis . Moreover, 12 lactylated proteins participated in fungal pathogenicity, suggesting a potential role for Kla in this process. Protein interaction network analysis suggested that a mass of protein interactions are regulated by lactylation. Together, our findings reveal widespread roles for lysine lactylation in regulating metabolism and melanin biosynthesis in P. verrucosa. Our data provide a rich resource for functional analyses of lactylation and facilitate the dissection of metabolic networks in this pathogen. The combined data sets represent the first report of the lactylome of P. verrucosa and provide a good foundation for further explorations of Kla in clinical fungal pathogens.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Fungi Phialophora Verrucosa

TISSUE(S): Fungal Sporangiophore

DISEASE(S): Phaeohyphomycosis

SUBMITTER: Yinggai Song  

LAB HEAD: Yinggai Song

PROVIDER: PXD032921 | Pride | 2022-10-15

REPOSITORIES: Pride

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Post-translational changes in <i>Phialophora verrucosa via</i> lysine lactylation during prolonged presence in a patient with a <i>CARD9</i>-related immune disorder.

Song Yinggai Y   Liu Xiao X   Stielow J Benjamin JB   de Hoog Sybren S   Li Ruoyu R  

Frontiers in immunology 20220808


<i>CARD9</i>-related inherited immune disorders are a major risk factor for chronic disseminated fungal infection. In addition to pathogens of <i>Candida</i> and dermatophytes, the environmental opportunists of the black yeast-like fungi are relatively frequent in this patient cohort. Particularly the genus <i>Phialophora</i> is overrepresented. We investigated two isolates of a strain of <i>P. verrucosa</i> residing in a <i>CARD9</i> patient, sampled with a period of ten years apart. Genomes, m  ...[more]

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