{"doi":"10.1101/2023.09.25.558961","title":"Deacetylation by sirtuins is important for <i>Aspergillus fumigatus</i> pathogenesis and virulence","abstract":"Abstract Protein acetylation is a crucial post-translational modification that controls gene expression and a variety of biological processes. Sirtuins, a prominent class of NAD + -dependent lysine deacetylases, serve as key regulators of protein acetylation and gene expression in eukaryotes. In this study, six single knockout strains of fungal pathogen Aspergillus fumigatus were constructed, in addition to a strain lacking all predicted sirtuins (SIRTKO). Phenotypic assays suggest that sirtuins are involved in cell wall integrity, secondary metabolite production, thermotolerance, and virulence. AfsirE deletion resulted in attenuation of virulence, as demonstrated in murine and Galleria infection models. The absence of AfSirE leads to altered acetylation status of proteins, including histones and non-histones, resulting in significant changes in the expression of genes associated with secondary metabolism, cell wall biosynthesis, and virulence factors. These findings encourage testing sirtuin inhibitors as potential therapeutic strategies to combat A. fumigatus infections or in combination therapy with available antifungals.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400893,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1178015,"name":"Gabriela Bassi da Silva","orcid":null,"position":1,"is_corresponding":false},{"id":1178016,"name":"Artur Honorato Reis","orcid":null,"position":2,"is_corresponding":false},{"id":1177591,"name":"Jaqueline Aline Gerhardt","orcid":"0000-0001-7443-6390","position":3,"is_corresponding":false},{"id":1177592,"name":"Everton Paschoal Antoniel","orcid":"0000-0002-8951-5531","position":4,"is_corresponding":false},{"id":1177593,"name":"Daniel Yuri Akiyama","orcid":"0000-0003-2859-1992","position":5,"is_corresponding":false},{"id":581697,"name":"Caroline Patini Rezende","orcid":"0000-0001-8263-6958","position":6,"is_corresponding":false},{"id":1177594,"name":"Leandro Xavier Neves","orcid":"0000-0002-6074-1025","position":7,"is_corresponding":false},{"id":745856,"name":"Elton J. R. Vasconcelos","orcid":"0000-0001-5130-6622","position":8,"is_corresponding":false},{"id":1177595,"name":"Fernanda Lopes de Figueiredo","orcid":"0000-0001-7697-2234","position":9,"is_corresponding":false},{"id":568670,"name":"Fausto Almeida","orcid":"0000-0002-3782-3698","position":10,"is_corresponding":false},{"id":565703,"name":"Patrícia Alves de Castro","orcid":"0000-0003-3045-6511","position":11,"is_corresponding":false},{"id":988231,"name":"Camila Figueiredo Pinzan","orcid":"0000-0001-7635-2107","position":12,"is_corresponding":false},{"id":317398,"name":"Gustavo H. Goldman","orcid":"0000-0002-2986-350X","position":13,"is_corresponding":false},{"id":1177596,"name":"Adriana Franco Paes Leme","orcid":"0000-0001-7959-147X","position":14,"is_corresponding":false},{"id":702305,"name":"Taícia Pacheco Fill","orcid":"0000-0003-4724-5251","position":15,"is_corresponding":false},{"id":424848,"name":"Nilmar Silvio Moretti","orcid":"0000-0003-0455-2497","position":16,"is_corresponding":false},{"id":565705,"name":"André Damásio","orcid":"0000-0001-9304-3998","position":17,"is_corresponding":false},{"id":1177590,"name":"Natália Sayuri Wassano","orcid":"0000-0003-2743-4549","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:08.195423Z","pmid":"37808717","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}