New Curcumin Analogue (PAC) Inhibits Candida albicans Virulence, Restricts Its Adhesion Potential, and Relieves Oral Epithelial Cell Inflammation and Defense Mechanisms
Abstract
:1. Introduction
2. Results
2.1. PAC Impairs Viability Together with Restricting Candida Growth and Colony Formation
2.2. PAC Compromises Biofilm Formation and Modifies Matrix Composition
2.3. PAC Ensures C. albicans Conversion to a Less Virulent Phenotype
2.4. PAC Alters Pathogen Adhesion Potential
2.5. PAC Controls C. albicans Growth Through Necrotic and ROS Pathways
2.6. PAC Relieves Gingival Epithelial Cells’ Defense Mechanisms
3. Discussion
4. Materials and Methods
4.1. Candida Strain and Epithelial Cell Culture
4.2. C. albicans Growth Assay
4.3. MTT Viability and Proliferation Assay
4.4. Colony Formation
4.5. Biofilm Formation by Transmission Electron Microscopy
4.6. Assessment of Morphological Transition
4.7. pH Measurement
4.8. Measurement of Biofilm Matrix Composition: Total Sugars
4.9. Quantitative Real-Time RT-PCR
4.10. Adhesion to Host Cells
4.11. Cell Viability Analysis by Propidium Iodide (PI) Staining
4.12. Reactive Oxygen Species (ROS) Analysis by Flow Cytometry
4.13. ELISA Assay
4.14. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
PAC | 3,5-Bis(4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone |
C. albicans | Candida albicans |
SAPs | Secreted aspartyl proteases |
HWP1 | Hyphal wall protein 1 |
EAP1 | Epithelial adhesin protein 1 |
RT-PCR | Reverse transcription polymerase chain reaction |
NF-κB | Nuclear factor kappa-light-chain-enhancer of activated B cells |
p38 | p38 mitogen-activated protein kinases |
JNK | c-Jun N-terminal kinase |
IL-6, IL-8, IL-1β | Interleukin-6, Interleukin-8, Interleukin-1 beta |
hBD | Human beta-defensin |
AMB | Amphotericin B |
RPMI | Roswell Park Memorial Institute medium |
DMSO | Dimethyl sulfoxide |
FBS | Fetal bovine serum |
MTT | 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide |
SEM | Scanning electron microscopy |
XTT | 2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[carbonyl(phenylamino)]-2H-tetrazolium hydroxide |
PBS | Phosphate-buffered saline |
DMEM | Dulbecco’s Modified Eagle Medium |
FBS | Fetal bovine serum |
TLR4 | Toll-like receptor 4 |
CD284 | Cluster of differentiation 284 (TLR4 marker) |
FITC | Fluorescein isothiocyanate |
RNA | Acide ribonucléique |
DNA | Acide désoxyribonucléique |
cDNA | ADN complémentaire |
PCR | Polymerase chain reaction |
Ct | Cycle threshold |
bp | Base pair |
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Gene for Candida | Primer Sequence (5′-3′) | Amp Size (bp) |
---|---|---|
HWP1 | Forward-GACCGTCTACCTGTGGGACAGT Reverse-GCTCAACTTATTGCTATCGCTTATTACA | 67 |
EAP1 | Forward-CTGCTCACTCAACTTCAATTGTCG Reverse -GAACACATCCACCTTCGGGA | 51 |
SAP1 | Forward-TTTCATCGCTCTTGCTATTGCTT Reverse -TGACATCAAAGTCTAAAGTGACAAAACC | 86 |
SAP2 | Forward-TCCTGATGTTAATGTTGATTGTCAAG Reverse -TGGATCATATGTCCCCTTTTGTT | 82 |
SAP3 | Forward-GGACCAGTAACATTTTTATGAGTTTTGAT Reverse -TGCTACTCCAACAACTTTCAACAAT | 87 |
SAP4 | Forward-AGATATTGAGCCCACAGAAATTCC Reverse -CAATTTAACTGCAACAGGTCCTCTT | 81 |
SAP5 | Forward-CATTGTGCAAAGTAACTGCAACAG Reverse -CAGAATTTCCCGTCGATGAGA | 77 |
SAP6 | Forward-CCTTTATGAGCACTAGTAGACCAAACG Reverse -TTACGCAAAAGGTAACTTGTATCAAGA | 101 |
SAP7 | Forward: 5′-GAAATGCAAAGAGTATTAGAGTTATTAC Reverse: GAATGATTTGGTTTACATCATCTTCAACTG | 196 |
SAP8 | Forward: TCCCTGAAGACATTGATAAAAGAGC-3′ Reverse: AGAATCAACCACCCATAAATCAGAA-5′ | 278 |
SAP9 | Forward-ATTTACTCCACAGTTTATCACTGAAGGT Reverse -CCACAAGAACCACCCTCAGTT | 86 |
SAP10 | Forward -CCCGGTATCCAATAGAATCGAA Reverse-TCAGTGAATGTGACGAATTTGAAGA | 78 |
ACT1 | Forward-GCTGGTAGAGACTTGACCAACCA-3′ Reverse: GACAATTTCTCTTTCAGCACTAGTAGTGA | 87 |
GMSM-K Genes | Primer Sequence (5′-3′) | Size (bp) |
---|---|---|
IL-1β | Forward: CTGTCCTGCGTGTTGAAAGA Reverse: TTGGGTAATTTTTGGGATCTACA | 69 |
IL-6 | Forward: TCTCCACAAGCGCCTTCG Reverse: CTCAGGGCTGAGATGCCG | 203 |
IL-8 | Forward: TTGGCAGCCTTCCTGATT Reverse: AACTTCTCCACAACCCTCTG | 248 |
hBD-1 | Forward: GCCTCTCCCCAGTTCCTGAA Reverse: GCAGAGAGTAAACAGCAGAAGGTA | 82 |
hBD-2 | Forward: TGTGGTCTCCCTGGAACAAAAT Reverse: GTCGCACGTCTCTGATGAGG | 105 |
hBD-3 | Forward: CTTCTGTTTGCTTTGCTCTTCCT Reverse: CTGTTCCTCCTTTGGAAGGCA | 138 |
hBD-4 | Forward: CACTCTACCAACACGCACCTAG Reverse: CGCAACTGGAACCACACACT | 133 |
GAPDH | Forward: GGTATCGTCGAAGGACTCATGAC Reverse: ATGCCAGTGAGCTTCCCGTTCAGC | 180 |
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Mezni, G.; Issa, H.; Dahdah, M.; Poulin, A.; Daïch, A.; Alamri, A.; Rouabhia, M.; Semlali, A. New Curcumin Analogue (PAC) Inhibits Candida albicans Virulence, Restricts Its Adhesion Potential, and Relieves Oral Epithelial Cell Inflammation and Defense Mechanisms. Antibiotics 2025, 14, 495. https://doi.org/10.3390/antibiotics14050495
Mezni G, Issa H, Dahdah M, Poulin A, Daïch A, Alamri A, Rouabhia M, Semlali A. New Curcumin Analogue (PAC) Inhibits Candida albicans Virulence, Restricts Its Adhesion Potential, and Relieves Oral Epithelial Cell Inflammation and Defense Mechanisms. Antibiotics. 2025; 14(5):495. https://doi.org/10.3390/antibiotics14050495
Chicago/Turabian StyleMezni, Ghazoua, Hawraa Issa, Manal Dahdah, Anaïs Poulin, Adam Daïch, Abdulaziz Alamri, Mahmoud Rouabhia, and Abdelhabib Semlali. 2025. "New Curcumin Analogue (PAC) Inhibits Candida albicans Virulence, Restricts Its Adhesion Potential, and Relieves Oral Epithelial Cell Inflammation and Defense Mechanisms" Antibiotics 14, no. 5: 495. https://doi.org/10.3390/antibiotics14050495
APA StyleMezni, G., Issa, H., Dahdah, M., Poulin, A., Daïch, A., Alamri, A., Rouabhia, M., & Semlali, A. (2025). New Curcumin Analogue (PAC) Inhibits Candida albicans Virulence, Restricts Its Adhesion Potential, and Relieves Oral Epithelial Cell Inflammation and Defense Mechanisms. Antibiotics, 14(5), 495. https://doi.org/10.3390/antibiotics14050495