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Lysine acetylation as drug target in fungi: an underexplored potential in Aspergillus spp.

  • Clinical Microbiology - Review
  • Published:
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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.

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Funding

The authors acknowledge the São Paulo Research Foundation (FAPESP) for the grants and fellowships provided (2017/22669-0 to AD; 2018/09948-0 to NSM). The authors also acknowledge the National Council for Scientific and Technological Development (CNPq) for the financial support (404654/2018-5 and 304816/2017-5 to AD; 424729/2018-0 to NSM; 123313/2018-0 to ABL). The authors acknowledge the Espaço da Escrita – Pró-Reitoria de Pesquisa – UNICAMP – for the language services provided.

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  1. Natália Sayuri Wassano and Ariely Barbosa Leite contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil

    Natália Sayuri Wassano & André Damasio

  2. Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil

    Ariely Barbosa Leite & Nilmar S. Moretti

  3. Department of Clinical Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil

    Franqueline Reichert-Lima & Angelica Zaninelli Schreiber

  4. Experimental Medicine Research Cluster (EMRC), University of Campinas (UNICAMP), Campinas, SP, Brazil

    André Damasio

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Wassano, N.S., Leite, A.B., Reichert-Lima, F. et al. Lysine acetylation as drug target in fungi: an underexplored potential in Aspergillus spp.. Braz J Microbiol 51, 673–683 (2020). https://doi.org/10.1007/s42770-020-00253-w

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