Fungal Lysine Deacetylases in Virulence, Resistance, and Production of Small Bioactive Compounds
Abstract
1. Introduction
2. The Fungal KDAC Repertoire: More Than Just the Number of Enzymes
3. The Role of Lysine Deacetylases in Fungal Pathogenicity and as Drug Targets for Novel Antifungal Agents
3.1. KDACs as Virulence Determinants of Human Fungal Pathogens
3.2. Putative KDAC Targets Involved in Virulence and Antifungal Resistance
- Is the virulence phenotype a result of changed gene expression patterns caused by altered chromatin regulation (i.e., hyperacetylation of histone tails at specific genomic loci like those coding for virulence factors or other proteins critical for fungal fitness)?
- Are (hyper)acetylated transcription factors of such critical genes responsible for the altered virulence behavior?
- Is a single or are multiple (hyper)acetylated protein(s) contributing to attenuated virulence?
- Is it a multifactorial process (i.e., a combination of the aforementioned points)?
3.3. KDACs as Modulators of Fungal Drug Resistance
3.4. KDAC Inhibitors for the Treatment of Invasive Fungal Infections
3.5. Targeting Protein–Protein Interaction within KDAC Complexes: Another Possibility to Combat Fungal Infections?
4. Lysine Deacetylases as Regulators of Small Fungal Natural Products
4.1. Impact of KDACs in the Regulation of SM Production: First Evidence
4.2. Versatile Functions of KDACs in the Expression of SMs: First Functional Hypothesis
4.3. Teamwork: KDACs Are Rarely Acting Alone
4.4. Pan KDAC Inhibitors for Mining New SMs: Quick and Easy but Not Always Valid
4.5. Deletion of KDACs or Their Complex Partners for Mining New SMs: Reliable but Elaborate and Not Always Feasible
4.6. An Alternative Approach: Depletion of (Essential) KDACs via the Promoter Rundown Technique
4.7. Microbial Interactions and the Induction of SMs: Are KDACs Involved in a Biochemical Warfare for Resources?
5. Concluding Remarks and Perspectives
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Pathogen | Rpd3 Homolog | Hos2 Homolog | Hda1 Homolog |
---|---|---|---|
Aspergillus fumigatus | RpdA (Afu2g03390)/ KD 1/av 2/mouse [89] | HosA (Afu2g03810) n.d. 3 | HdaA (Afu5g01980)/ KO/fv/mouse [95] |
Candida albicans | Rpd31 (C3_07000W_A) KO/av/mouse [70] | Hos2 (C3_00780W_A) n.d. | Hda1 (CR_02050C_A) n.d. |
Cryptococcus neoformans | Rpd302 (CNAG_05096) KO/att/mouse [34] Rpd303 (CNAG_05276) KO/att/mouse [34] Rpd304 (CNAG_05690) KO/att/mouse [92] | Hos2 (CNAG_05563) KO/att/mouse [34] | Hda1 (CNAG_01563) KO/av/mouse [94] KO/att/mouse [34] |
Beauveria bassiana | Rpd3 (EJP69682.1) KO/att/Galleria [84] | Hos2 (XP_008603650.1) KO/att/Galleria [85] | Hda1/Clr3 (EJP66596.1) n.d. |
Botrytis cinerea | Rpd3 (Bcin05g02590) OE/att/tomato [64] | Hos2 (Bcin01g03610) n.d. | Hda1 (Bcin15g02130) n.d. |
Cochliobolus carbonum | Hdc2 (AAK35180.1) n.d. | Hdc1 (AAL56814.1) KO/att/maize [49] | AAP95014.1 n.d. |
Fusarium graminearum | Rpd3/Hda3 (FGRAMPH1_01G01959) KO/av/wheat [77] | Hdf1/Hda2 (FGRAMPH1_01G03337) KO/att/wheat, corn [76] | Hdf2/Hda1 (FGRAMPH1_01G15009) n.d. |
Ustilago maydis | Hda1 (U6MAG_02065) KO/fv/maize [32] KO/fv/maize [83] Hda2 (UMAG_11308) KO/fv/maize [83] | Hos2 (UMAG_11828) KO/att/maize [83] | Hda1/Clr3 (UMAG_02102) KO/att/maize [83] |
Magnaporthe oryzae | Rpd3 (MGG_05857) OE/av/rice, barley [82] | Hos2 (MGG_01633) KO/av/rice, barley [63] KO/att/rice [79] | Hda1 (MGG_01076) KO/att/rice [80] |
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Bauer, I.; Graessle, S. Fungal Lysine Deacetylases in Virulence, Resistance, and Production of Small Bioactive Compounds. Genes 2021, 12, 1470. https://doi.org/10.3390/genes12101470
Bauer I, Graessle S. Fungal Lysine Deacetylases in Virulence, Resistance, and Production of Small Bioactive Compounds. Genes. 2021; 12(10):1470. https://doi.org/10.3390/genes12101470
Chicago/Turabian StyleBauer, Ingo, and Stefan Graessle. 2021. "Fungal Lysine Deacetylases in Virulence, Resistance, and Production of Small Bioactive Compounds" Genes 12, no. 10: 1470. https://doi.org/10.3390/genes12101470
APA StyleBauer, I., & Graessle, S. (2021). Fungal Lysine Deacetylases in Virulence, Resistance, and Production of Small Bioactive Compounds. Genes, 12(10), 1470. https://doi.org/10.3390/genes12101470