Psd1 Effects on Candida albicans Planktonic Cells and Biofilms

Gonçalves, Sónia; Silva, Patrícia M.; Felício, Mário R.; Medeiros, Luciano Neves de; Kurtenbach, Eleonora; Santos, Nuno C.

doi:10.3389/fcimb.2017.00249

Cited by 53 publications

(47 citation statements)

References 63 publications

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“…Those cell deformations might be linked to leakage of cellular contents as a result of cell membrane damage. Comparable effects were observed in other AFM studies describing alterations in C. albicans cell morphology and membrane integrity when in the presence of antimicrobial peptides Psd1 46 and LL-37 47 . TEM of C. albicans treated with ToAP2 revealed several cells showing a loss of cell wall integrity and presenting an internal amorphous cytoplasm with mostly no distinguishable organelles, suggesting that this AMP can induce damage not only on the plasma membrane but also in the membrane of cellular organelles inducing loss of integrity of those structures.…”

Section: Discussionsupporting

confidence: 74%

Mechanisms of action of antimicrobial peptides ToAP2 and NDBP-5.7 against Candida albicans planktonic and biofilm cells

Dias

Silva

Araújo

et al. 2020

Sci Rep

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Candida albicans is a major cause of human infections, ranging from relatively simple to treat skin and mucosal diseases to systemic life-threatening invasive candidiasis. Fungal infections treatment faces three major challenges: the limited number of therapeutic options, the toxicity of the available drugs, and the rise of antifungal resistance. In this study, we demonstrate the antifungal activity and mechanism of action of peptides ToAP2 and NDBP-5.7 against planktonic cells and biofilms of C. albicans. Both peptides were active against C. albicans cells; however, ToAP2 was more active and produced more pronounced effects on fungal cells. Both peptides affected C. albicans membrane permeability and produced changes in fungal cell morphology, such as deformations in the cell wall and disruption of ultracellular organization. Both peptides showed synergism with amphotericin B, while ToAP2 also presents a synergic effect with fluconazole. Besides, ToAP2 (6.25 µM.) was able to inhibit filamentation after 24 h of treatment and was active against both the early phase and mature biofilms of C. albicans. Finally, ToAP2 was protective in a Galleria mellonella model of infection. Altogether these results point to the therapeutic potential of ToAP2 and other antimicrobial peptides in the development of new therapies for C. albicans infections. Candida albicans is a fungal species present in the normal human microbiota, colonizing several areas of the body. However, under certain circumstances, this species may become a pathogen, causing diseases that can be life-threatening 1-4. The use of broad-spectrum antibiotics, immune suppression, or changes in the local host environments are examples of situations that may favor the proliferation of C. albicans and the onset of disease 5-8. Moreover, C. albicans ability to thrive in human tissues involves metabolic and morphological changes associated with the expression of different virulence factors 9. C. albicans virulence factors include secretion of enzymes, adhesion to cell surfaces and evasion of the immune system 10,11. Two virulence factors of major clinical importance are the fungal polymorphism and its ability to form biofilms 12-14. C. albicans ability to transit between yeast and filamentous forms is crucial for pathogenesis and both fungal forms are relevant for infection 15. For instance, hyphae have a major role on tissue invasion, whereas the yeast morphology facilitates fungal dispersion 16. The different fungal morphologies are also important for the formation of C. albicans biofilms 17. Living in biofilms confers to the microorganisms several advantages, when compared to the planktonic lifestyle, including protection against immune cells, increased resistance to antimicrobials agents and other chemical, physical and environmental stressors 18,19 .

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Section: Discussionsupporting

confidence: 74%

Mechanisms of action of antimicrobial peptides ToAP2 and NDBP-5.7 against Candida albicans planktonic and biofilm cells

Dias

Silva

Araújo

et al. 2020

Sci Rep

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“…Biofilm was then quantified by the crystal violet method (as described above) in presence and absence of antibiotic in triplicate. This method is similar to that described 41 for determining the effect of antifungal agents in the biofilm phase. RNA was extracted from C. albicans L-391/2015 in the biofilm phase by allowing the organisms to grow on a Petri plate for 48 hours at 308C as described above.…”

Section: Antifungal Susceptibility Of C Albicans L-391/2015 Before Amentioning

confidence: 99%

Temporal Expression of Genes in Biofilm-Forming Ocular Candida albicans Isolated From Patients With Keratitis and Orbital Cellulitis

Ranjith

Chakravarthy

Adicherla

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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Citation: Ranjith K, Kalyana Chakravarthy S, Adicherla H, Sharma S, Shivaji S. Temporal expression of genes in biofilm-forming ocular Candida albicans isolated from patients with keratitis and orbital cellulitis. Invest Ophthalmol Vis Sci. 2018;59:528-538. https://doi.org/ 10.1167/iovs.17-22933 PURPOSE. To study antibiotic susceptibility and biofilm-forming potential of ocular isolates of Candida albicans along with gene expression. METHODS.Seven clinical isolates of C. albicans (keratitis-6 and orbital cellulitis-1) were evaluated. Biofilm formation in one isolate was monitored by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Expression of 27 genes (real-time PCR) associated with biofilm formation and virulence was compared between biofilm-positive and biofilm-negative ocular C. albicans isolates. The temporal expression (4 to 72 hours) of the 27 overexpressed genes was also determined. Similar studies were also done with biofilmpositive and biofilm-negative nonocular C. albicans.RESULTS. Four of seven ocular C. albicans isolates exhibited the potential to form biofilm, one of which was resistant to three antifungals, whereas three were susceptible to all. SEM studies indicated that biofilm increased from two to three adherent layers of cells at 24 hours to multiple layers by 72 hours. CLSM showed that biofilm thickness increased from 5.2 lm at 24 hours to 17.98 lm at 72 hours. Upregulation of 27 genes involved in virulence and biofilm formation was observed both in the ocular and nonocular C. albicans positive for biofilm formation and compared to the respective non-biofilm-forming C. albicans. The results also indicated similarity in expression of genes between biofilm-forming ocular and nonocular pathogenic C. albicans. Temporal expression of the 27 genes (involved in adhesion, initiation, maturation, and dispersal stages of biofilm) in the biofilm-positive ocular isolate indicated that expression pattern followed four different patterns.CONCLUSIONS. This is the first study showing similarity in expression of genes in biofilmforming ocular and nonocular isolates of C. albicans, suggesting that upregulated genes could serve as a potential target for developing therapeutic strategies.

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“…Pisum sativum defensin 1 (Psd1) is a 46-amino acid residue plant defensin isolated from pea seeds that presents well-documented antimicrobial activity against several fungal species [4,7,[15][16][17]. The mechanism of action proposed for Psd1 antifungal activity includes its interaction with specific cell wall/membrane lipid targets, such as C8-desaturated and C9-methylated glucosylceramide (GlcCer), a fungal exclusive GSL, and ergosterol [8,11,16].…”

Section: Introductionmentioning

confidence: 99%

Pisum sativum Defensin 1 Eradicates Mouse Metastatic Lung Nodules from B16F10 Melanoma Cells

Amaral

Santos

Andrade

et al. 2020

IJMS

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Psd1 is a pea plant defensin which can be actively expressed in Pichia pastoris and shows broad antifungal activity. This activity is dependent on fungal membrane glucosylceramide (GlcCer), which is also important for its internalization, nuclear localization, and endoreduplication. Certain cancer cells present a lipid metabolism imbalance resulting in the overexpression of GlcCer in their membrane. In this work, in vitroassays using B16F10 cells showed that labeled fluorescein isothiocyanate FITC-Psd1 internalized into live cultured cells and targeted the nucleus, which underwent fragmentation, exhibiting approximately 60% of cells in the sub-G0/G1 stage. This phenomenon was dependent on GlcCer, and the participation of cyclin-F was suggested. In a murine lung metastatic melanoma model, intravenous injection of Psd1 together with B16F10 cells drastically reduced the number of nodules at concentrations above 0.5 mg/kg. Additionally, the administration of 1 mg/kg Psd1 decreased the number of lung inflammatory cells to near zero without weight loss, unlike animals that received melanoma cells only. It is worth noting that 1 mg/kg Psd1 alone did not provoke inflammation in lung tissue or weight or vital signal losses over 21 days, inferring no whole animal cytotoxicity. These results suggest that Psd1 could be a promising prototype for human lung anti-metastatic melanoma therapy.

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Psd1 Effects on Candida albicans Planktonic Cells and Biofilms

Cited by 53 publications

References 63 publications

Mechanisms of action of antimicrobial peptides ToAP2 and NDBP-5.7 against Candida albicans planktonic and biofilm cells

Mechanisms of action of antimicrobial peptides ToAP2 and NDBP-5.7 against Candida albicans planktonic and biofilm cells

Temporal Expression of Genes in Biofilm-Forming Ocular Candida albicans Isolated From Patients With Keratitis and Orbital Cellulitis

Pisum sativum Defensin 1 Eradicates Mouse Metastatic Lung Nodules from B16F10 Melanoma Cells

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