Anti-Biofilm Activity of Cannabidiol against Candida albicans
Abstract
:1. Introduction
2. Materials and Methods
2.1. CBD
2.2. Fungal Strains and Growth Conditions
2.3. C. albicans Biofilm Formation
2.4. Morphological Studies
2.5. Determination of Minimal Inhibitory Concentration (MIC)
2.6. Determination of Minimal Fungicidal Concentration (MFC)
2.7. Determination of Chitin Content in Biofilms
2.8. Confocal Laser Scanning Microscopy (CLSM) of Biofilms
2.9. Assessment of Mitochondrial Function
2.10. Effect of CBD on Intracellular ATP Levels in Biofilm
2.11. Effect of CBD on ROS Accumulation
2.12. Evaluation of Membrane Permeability of Biofilm Cells
2.13. Quantitative Real Time RT-PCR Analysis of C. albicans Specific Genes
2.14. Statistical Analysis
3. Results
3.1. CBD Inhibits Biofilm Formation of Candida Albicans
3.2. CBD Disrupts Mature Biofilm
3.3. CBD Alters Biofilm Morphology and Fungal Cell Structure
3.4. CBD Alters Mitochondrial Activity and Elevates Intracellular Reactive Oxygen Species (ROS)
3.5. CBD Causes Membrane Damage to the Fungi in Biofilm
3.6. CBD Differentially Affects Gene Expression in Fungal Biofilm
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | Fold Change | SEM a | Description and Function b |
---|---|---|---|
adh5 | −2.69 | 0.04 | Putative alcohol dehydrogenase; production of extracellular matrix |
big1 | −3.75 | 0.12 | Endoplasmic reticulum protein; required for beta-1,6-glucan synthesis, filamentation, adhesion, and virulence |
FKS1 | −1.41 | 0.02 | Essential beta-1,3-glucan synthase subunit; beta-1,3-glucan is the main component of extracellular matrix |
ece1 | −2.96 | 0.01 | Candidalysin, cytolytic peptide toxin essential for mucosal infection; hypha-specific |
hwp1 | −1.46 | 0.05 | Hyphal cell wall protein; hypha-specific |
eed1 | −6.21 | 0.28 | RNA polymerase II regulator; filamentation |
efg1 | −1.64 | 0.02 | bHLH transcription factor; hyphal growth, cell-wall gene regulation; roles in adhesion, virulence |
ras1 | −1.66 | 0.07 | Regulates cAMP and MAP kinase pathways; role in hyphal induction, virulence, apoptosis |
ALS3 | −1.72 | 0.06 | Cell wall adhesin; hyphal-specific |
chs1 | −2.54 | 0.12 | Chitin synthase; essential; for primary septum synthesis in yeast and hyphae |
cht1 | −3.73 | 0.15 | Chitinase; putative N-terminal catalytic domain; has secretory signal sequence |
cht2 | −1.75 | 0.01 | GPI-linked chitinase; required for normal filamentous growth |
cht3 | −7.99 | 0.23 | Major chitinase; cell separation |
erg11 | −3.37 | 0.23 | Lanosterol 14-alpha-demethylase; ergosterol biosynthesis |
erg20 | −3.32 | 0.10 | Putative farnesyl pyrophosphate synthetase involved in isoprenoid and sterol biosynthesis |
lip2 | −2.82 | 0.05 | Secreted lipase; hydrolysis and synthesis of triacylglycerols |
lip4 | −1.59 | 0.04 | Secreted lipase |
lip5 | −1.55 | 0.10 | Cold-activated secreted lipase |
plb1 | −1.46 | 0.22 | Phospholipase B; host cell penetration and virulence in mouse systemic infection |
plb2 | −3.03 | 0.06 | Putative phospholipase B; tissue degradation, hyphal formation, and host invasion, hydrolytic activity |
rbt1 | −2.90 | 0.17 | Cell wall protein with similarity to Hwp1; hypha-specific |
rbt4 | −3.93 | 0.30 | Plant pathogenesis-related protein, may damage either host cells or competing microbes; hypha-specific |
rbt5 | −3.04 | 0.01 | GPI-linked cell wall protein; hemoglobin utilization; required for RPMI biofilms |
pra1 | −9.47 | 0.70 | Cell surface protein that sequesters zinc from host tissue; enriched at hyphal tips; released extracellularly |
sod1 | −3.44 | 0.04 | Cytosolic copper- and zinc-containing superoxide dismutase; antioxidant defense |
sod2 | −2.55 | 0.10 | Mitochondrial Mn-containing superoxide dismutase; protection against oxidative stress |
sod4 | −2.39 | 0.05 | Cu-containing superoxide dismutase; antioxidant defense |
trr1 | −7.98 | 0.15 | Thioredoxin reductase; antioxidant defense |
vcx1 | −2.80 | 0.11 | Putative H+/Ca2+ antiporter; tolerance and virulence through calcineurinand Ca2+/H+ exchanger |
Gene | Fold Change | SEM a | Description and Function b |
---|---|---|---|
HSP104 | 2.29 | 0.02 | Heat-shock protein; heat shock/stress induced |
HSP70 | 2.25 | 0.03 | Heat-shock protein; heat shock/stress induced, response to toxic substance |
HSP90 | 2.65 | 0.05 | Heat-shock protein; cellular response to drug, negative regulation of filamentous growth, key regulator of biofilm dispersion |
YWP1 | 40.25 | 0.11 | Secreted yeast wall protein; antiadhesive effect, yeast-specific |
DPP3 | 3.05 | 0.15 | Required for farnesol biosynthesis |
Gene | Forward Primer | Reverse Primer |
---|---|---|
act1 | AAGAATTGATTTGGCTGGTAGAGA | TGGCAGAAGATTGAGAAGAAGTTT |
adh5 | ACCTGCAAGGGCTCATTCTG | CGGCTCTCAACTTCTCCATA |
als3 | TAATGCTGCTACGTATAATT | CCTGAAATTGACATGTAGCA |
big1 | TTATTCGTCCTACTAGCAT | CATATTTGTCACCGAAGTAA |
chs1 | CTGACAAGAGCCAACACTGC | CGCCTCTTGATGGTGATGAT |
cht1 | CCTGTTGCTGCTACTACTAC | TTGTAGCATTTGGCTGCCCA |
cht2 | GCACCAAATACGTCACCATTG | GAAGGCAAAGGCAGCCAATAA |
cht3 | GTATTTCCAAATCCAGTTC | GTCAATATTTGATAAGTCG |
dpp3 | TTATCTGTAATTATCATTGT | GTTGTCAAACTTCAATTGA |
ece1 | GCTGGTATCATTGCTGATAT | TTCGATGGATTGTTGAACAC |
eed1 | AGCAACGACTTCCAAAAGGA | CGGTTTCTGGTTCGATGATT |
efg1 | TATGCCCCAGCAAACAACTG | TTGTTGTCCTGCTGTCTGTC |
erg11 | AAGAATCCCTGAAACCAA | CAGCAGCAGTATCCCATC |
erg20 | TTACCCGTGGCATTAGCAATGTA | TCCCAAGGGAATCAAAATGTCTC |
fks1 | CGTGAAATTGATCATGCCTGTAC | AACCCTTCTGGGCTCCAAA |
hsp70 | TGCCGTTGTTACCGTTCCAGCTTA | AACCATAAGCAATGGCAGCAGCAG |
hsp90 | GCTTTAAGTGCTGGTGCTGACGTT | TGGTACCACGACCCAATCTTTCGT |
hsp104 | ACGGCCATACTCTGTGGTCTTGTT | CGGCATTGATGTAGTTTGCACCCA |
hwp1 | CACAGGTAGACGGTCAAGGT | AAGGTTCTTCCTGCTGTTGT |
lip2 | GGCCTGGATTGATGCAAGAT | TTGTGTGCAGACATCCTTGGA |
lip4 | GCGCTCCTGTTGCTTTGACT | ACACGGTTTGTTTTCCATTGAA |
lip5 | TGGTTCCAAAAATACCCGTGTT | CGACAATAGGGACGATTTGATCA |
plb1 | GGTGGAGAAGATGGCCAAAA | AGCACTTACGTTACGATGCAACA |
plb2 | TGAACCTTTGGGCGACAACT | GCCGCGCTCGTTGTTAA |
pra1 | GCTTTGGATGTGTATGCATATG | CTAGGGTTGCTATCGGTATGTG |
ras1 | GGCCATGAGAGAACAATATA | GTCTTTCCATTTCTAAATCAC |
rbt1 | CTGCAAAAACAGTGCTCTCG | CAAGAATGCAGCAAGACCAA |
rbt4 | ATCGCCTATGTCACCCAGAC | CATTACCACCATCAGCATCG |
rbt5 | CTGCTAAAGAAACCACTGCTG | GCTTCAACGGAAACAGAAGC |
sod1 | TTGAACAAGAATCCGAATCC | AGCCAATGACACCACAAGCAG |
sod2 | ACCACCCGTGCTACTTTGAAC | GCCCATCCAGAACCTTGAAT |
sod4 | CCAGTGAATCATTTGAAGTTG | AGAAGCACTAGTTGATGAACC |
trr1 | TTTCTGCCTGTGCTGTTTGT | TTCCTGGAGTGGTTTGAATGTA |
vcx1 | CTTTGTCGCTGGTGGGATT | GCATCGGCACTTTGGTCT |
ywp1 | GCTACTGCTACTGGTGCTA | AACGGTGGTTTCTTGAC |
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Feldman, M.; Sionov, R.V.; Mechoulam, R.; Steinberg, D. Anti-Biofilm Activity of Cannabidiol against Candida albicans. Microorganisms 2021, 9, 441. https://doi.org/10.3390/microorganisms9020441
Feldman M, Sionov RV, Mechoulam R, Steinberg D. Anti-Biofilm Activity of Cannabidiol against Candida albicans. Microorganisms. 2021; 9(2):441. https://doi.org/10.3390/microorganisms9020441
Chicago/Turabian StyleFeldman, Mark, Ronit Vogt Sionov, Raphael Mechoulam, and Doron Steinberg. 2021. "Anti-Biofilm Activity of Cannabidiol against Candida albicans" Microorganisms 9, no. 2: 441. https://doi.org/10.3390/microorganisms9020441
APA StyleFeldman, M., Sionov, R. V., Mechoulam, R., & Steinberg, D. (2021). Anti-Biofilm Activity of Cannabidiol against Candida albicans. Microorganisms, 9(2), 441. https://doi.org/10.3390/microorganisms9020441