Lysine acetylation as drug target in fungi: an underexplored potential in Aspergillus spp.
- 1 June 2020
- journal article
- review article
- Published by Springer Science and Business Media LLC in Brazilian Journal of Microbiology
- Vol. 51 (2), 673-683
- https://doi.org/10.1007/s42770-020-00253-w
Abstract
In recent years, the intensification of the use of immunosuppressive therapies has increased the incidence of invasive infections caused by opportunistic fungi. Considering that, the spread of azole resistance and amphotericin B (AmB) inefficiency against some clinical and environmental isolates has been described. Thus, to avoid a global problem when controlling fungal infections and critical failures in medicine, and food security, new approaches for drug target identification and for the development of new treatments that are more effective against pathogenic fungi are desired. Recent studies indicate that protein acetylation is present in hundreds of proteins of different cellular compartments and is involved in several biological processes, i.e., metabolism, translation, gene expression regulation, and oxidative stress response, from prokaryotes and eukaryotes, including fungi, demonstrating that lysine acetylation plays an important role in essential mechanisms. Lysine acetyltransferases (KATs) and lysine deacetylases (KDACs), the two enzyme families responsible for regulating protein acetylation levels, have been explored as drug targets for the treatment of several human diseases and infections. Aspergilli have on average 8 KAT genes and 11 KDAC genes in their genomes. This review aims to summarize the available knowledge about Aspergillus spp. azole resistance mechanisms and the role of lysine acetylation in the control of biological processes in fungi. We also want to discuss the lysine acetylation as a potential target for fungal infection treatment and drug target discovery.Funding Information
- São Paulo Research Foundation (2017/22669-0, 2018/09948-0)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (404654/2018-5)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (304816/2017-5, 424729/2018-0, 123313/2018-0)
This publication has 132 references indexed in Scilit:
- The Spt-Ada-Gcn5 Acetyltransferase (SAGA) Complex in Aspergillus nidulansPLOS ONE, 2013
- Proteome-wide Analysis of Lysine Acetylation Suggests its Broad Regulatory Scope in Saccharomyces cerevisiaeMolecular & Cellular Proteomics, 2012
- Lysine Deacetylases Hda1 and Rpd3 Regulate Hsp90 Function thereby Governing Fungal Drug ResistanceCell Reports, 2012
- Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylationProceedings of the National Academy of Sciences of the United States of America, 2011
- Willow volatiles influence growth, development, and secondary metabolism in Aspergillus parasiticusApplied Microbiology and Biotechnology, 2011
- A Novel Motif in Fungal Class 1 Histone Deacetylases Is Essential for Growth and Development ofAspergillusMolecular Biology of the Cell, 2010
- HdaA, a class 2 histone deacetylase of Aspergillus fumigatus, affects germination and secondary metabolite productionFungal Genetics and Biology, 2009
- Structure and chemistry of the p300/CBP and Rtt109 histone acetyltransferases: implications for histone acetyltransferase evolution and functionCurrent Opinion in Structural Biology, 2008
- Fungal Rtt109 histone acetyltransferase is an unexpected structural homolog of metazoan p300/CBPNature Structural & Molecular Biology, 2008
- Histone modifications and chromatin dynamics: a focus on filamentous fungiFEMS Microbiology Reviews, 2008