Modulation of Virulence-Associated Traits in Aspergillus fumigatus by BET Inhibitor JQ1
Abstract
:1. Introduction
2. Materials and Methods
2.1. A. fumigatus Strain and Culture Conditions
2.2. Antifungal Susceptibility Testing
2.3. JQ1 Activity against Biofilm Formation and Mature Biofilm
2.4. Conidial Surface Hydrophobicity
2.5. Adhesion Assays
2.6. Microscopic Evaluation of Adhesion
2.7. Radial Growth Experiment
2.8. Protein Extraction and Quantification
2.9. Proteomic Profile by Liquid Chromatography-Mass Spectrometry (LC-MS/MS)
2.10. RNA Extraction and cDNA Production
2.11. Quantitative Real Time-PCR (qPCR) Analysis
2.12. Infection of G. mellonella Larvae
2.13. Toxicity of Extracellular Proteins in G. mellonella Larvae and Melanization Assay
2.14. Statistical Analysis
3. Results
3.1. JQ1 Shows Low Activity against A. fumigatus Planktonic Growth
3.2. JQ1 Affects the A. fumigatus Biofilm
3.3. JQ1 Decreases the Cell Surface Hydrophobicity
3.4. JQ1 Decreases the Cell Surface Adhesion
3.5. JQ1 Reduces the Radial Growth Rate of A. fumigatus
3.6. JQ1 Changes the Concentration of Extracellular Virulence Proteins
3.7. JQ1 Reduces the Protein Related to Melanin Synthesis
3.8. JQ1 Reduces the Gene Expression of Extracellular and Intracellular Virulence Factors
3.9. JQ1 Reduces the Mortality of G. mellonella Larvae Infected with A. fumigatus
3.10. Pretreatment of A. fumigatus with JQ1 Reduces the Mortality in G. mellonella Model
3.11. The Toxicity of Extracellular Protein in G. mellonella Larvae was Reduced after Treatment of A. fumigatus with JQ1
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene Name | Primer | Nucleotide Sequence | GenBank |
---|---|---|---|
AFUA_1G06390 (Elongation factor-1) | EF1-F | 5′-AGGTCATCGTCCTCAACCAC-3′ | XM_745295.2 |
EF1-R | 5′-ACCGGACTTGATGAACTTGG-3′ | ||
AFUA_2G17530 (Conidial pigment biosynthesis oxidase ABR2) | ABR-F | 5′-CAATCAAAGAGGCCAAGGAG-3′ | KAH1289617.1 |
ABR-R | 5′-TATGGCAGTGCAACAGGAAC-3′ | ||
AFUA_1G11640 (Superoxide dismutase putative) | SOD-F | 5′-TCTCCCACATAGACAGAACACG-3′ | KAF4252661.1 |
SOD-R | 5′-ATGCTAGGGCTTCATTGTCG-3′ | ||
AFUA_1G16600 (Ribonuclease T2 putative) | RB-F | 5′-GCTGCTGTCCTACATGCAAA-3′ | KAH2174949.1 |
RB-R | 5′-GGCCCTTGAAAAGATCAACA-3′ | ||
AFUA_3G11280 (Chitinase class V chitinase, putative) | CHIT-F | 5′-TTTACGGCTGCATCAAACAG-3′ | KAH2766398.1 |
CHIT-R | 5′-GAGCCTCAACTTCGTTCTGG-3′ |
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Orekhova, A.; De Angelis, M.; Cacciotti, A.; Reverberi, M.; Rotili, D.; Giorgi, A.; Protto, V.; Bonincontro, G.; Fiorentino, F.; Zgoda, V.; et al. Modulation of Virulence-Associated Traits in Aspergillus fumigatus by BET Inhibitor JQ1. Microorganisms 2022, 10, 2292. https://doi.org/10.3390/microorganisms10112292
Orekhova A, De Angelis M, Cacciotti A, Reverberi M, Rotili D, Giorgi A, Protto V, Bonincontro G, Fiorentino F, Zgoda V, et al. Modulation of Virulence-Associated Traits in Aspergillus fumigatus by BET Inhibitor JQ1. Microorganisms. 2022; 10(11):2292. https://doi.org/10.3390/microorganisms10112292
Chicago/Turabian StyleOrekhova, Anastasia, Marta De Angelis, Andrea Cacciotti, Massimo Reverberi, Dante Rotili, Alessandra Giorgi, Virginia Protto, Graziana Bonincontro, Francesco Fiorentino, Victor Zgoda, and et al. 2022. "Modulation of Virulence-Associated Traits in Aspergillus fumigatus by BET Inhibitor JQ1" Microorganisms 10, no. 11: 2292. https://doi.org/10.3390/microorganisms10112292
APA StyleOrekhova, A., De Angelis, M., Cacciotti, A., Reverberi, M., Rotili, D., Giorgi, A., Protto, V., Bonincontro, G., Fiorentino, F., Zgoda, V., Mai, A., Palamara, A. T., & Simonetti, G. (2022). Modulation of Virulence-Associated Traits in Aspergillus fumigatus by BET Inhibitor JQ1. Microorganisms, 10(11), 2292. https://doi.org/10.3390/microorganisms10112292