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

Author(s)

Wassano, Natalia Sayuri ^[1] ; Leite, Ariely Barbosa ^[2] ; Reichert-Lima, Franqueline ^[3] ; Schreiber, Angelica Zaninelli ^[3] ; Moretti, Nilmar S. ^[2] ; Damasio, Andre ^{[1, 4]}

Affiliation

^[1] Univ Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP - Brazil

^[2] Fed Univ Sao Paulo UNIFESP, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP - Brazil

^[3] Univ Campinas Unicamp, Sch Med Sci, Dept Clin Pathol, Campinas, SP - Brazil

^[4] Univ Campinas UNICAMP, EMRC, Campinas, SP - Brazil

• Document type: Review article
• Source: Brazilian Journal of Microbiology; v. 51, n. 2 MAR 2020.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 17/22669-0 - N-glycosylation and enzymes secretion in filamentous fungi
• Grantee: André Ricardo de Lima Damasio
• Support Opportunities: Program for Research on Bioenergy (BIOEN) - Regular Program Grants
• FAPESP's process: 18/09948-0 - Study of protein acetylation in Leishmania
• Grantee: Nilmar Silvio Moretti
• Support Opportunities: Regular Research Grants