Farnesol, a Fungal Quorum-Sensing Molecule Triggers Candida Albicans Morphological Changes by Downregulating the Expression of Different Secreted Aspartyl Proteinase Genes

Décanis, Nadège; Tazi, Neftaha; Correia, Alexandra; Vilanova, Manuel; Rouabhia, Mahmoud

doi:10.2174/1874285801105010119

Cited by 40 publications

(29 citation statements)

References 48 publications

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“…In addition, Cope (1980) reported that fungistatic and fungicidal doses of miconazole interacted directly with the cellular components of C. albicans and resulted in an increase in the intracellular K + . Furthermore, farnesol modulated the morphogenesis of C. albicans through a downregulation of Saps 2, 4, 5, and 6 expressions (Décanis et al, 2011). However, Hultenby et al (2014) reported that treatment of C. albicans with a mixture of propylene glycol, lactic acid and urea resulted in certain ultrastructural changes but without a specific mode of action.…”

Section: Discussionmentioning

confidence: 99%

Miconazole-Urea in a Buccal Film as a New Trend for Treatment of Resistant Mouth Fungal White Patches

2018

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A growing concern about Candida albicans is the emergence of high incidence of resistance against antifungal agents, which requires searching for new medications or improving the response to the existing members. The objective of this work was to evaluate the effectiveness of the miconazole in the absence and presence of urea, as a penetration enhancer, against C. albicans. In addition to, formulating both of them in a polymer film to be used topically for treatment of mouth fungal white patches caused by C. albicans. A synergistic effect was recorded between this imidazole and urea against the test strain. Miconazole MIC (32 mg/L) was dramatically reduced to 0.0625 mg/L following combination with urea. Transmission electron microscopy explained the mechanisms of action mediated by the test agents. Minimal fungicidal dose of miconazole combined with urea showed early apoptotic cells with condensed chromatin and small blebs. Cytoplasmic leakage and necrosis in some cells was observed at high fungicidal dose. Buccal bioadhesive films were prepared using increasing values of the drug MIC and urea. The physicochemical characters of the prepared films including; film weight, thickness, swelling index, drug content, folding endurance, surface pH, bioadhesion force and time and drug release kinetics, were studied. Microbiological evaluation of all prepared films showed an increase in the inhibition zone diameters for films containing increasing concentrations of both miconazole and urea in a concentration-dependent manner (30–40 mm) compared to miconazole alone (18 mm). Based on our results, the prepared films are promising for buccal administration of miconazole/urea showing synergistic effect for treatment of C. albicans infection.

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Section: Discussionmentioning

confidence: 99%

Miconazole-Urea in a Buccal Film as a New Trend for Treatment of Resistant Mouth Fungal White Patches

2018

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“…Specific SAP genes were found to be preferentially expressed by Candida hyphal forms [10,15,59]. Because KSL-W downregulated C. albicans growth and transition, this may have occurred through a modulation of the SAP genes.…”

Section: Discussionmentioning

confidence: 99%

C. albicansgrowth, transition, biofilm formation, and gene expression modulation by antimicrobial decapeptide KSL-W

et al. 2013

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BackgroundAntimicrobial peptides have been the focus of much research over the last decade because of their effectiveness and broad-spectrum activity against microbial pathogens. These peptides also participate in inflammation and the innate host defense system by modulating the immune function that promotes immune cell adhesion and migration as well as the respiratory burst, which makes them even more attractive as therapeutic agents. This has led to the synthesis of various antimicrobial peptides, including KSL-W (KKVVFWVKFK-NH2), for potential clinical use. Because this peptide displays antimicrobial activity against bacteria, we sought to determine its antifungal effect on C. albicans. Growth, hyphal form, biofilm formation, and degradation were thus examined along with EFG1, NRG1, EAP1, HWP1, and SAP 2-4-5-6 gene expression by quantitative RT-PCR.ResultsThis study demonstrates that KSL-W markedly reduced C. albicans growth at both early and late incubation times. The significant effect of KSL-W on C. albicans growth was observed beginning at 10 μg/ml after 5 h of contact by reducing C. albicans transition and at 25 μg/ml by completely inhibiting C. albicans transition. Cultured C. albicans under biofilm-inducing conditions revealed that both KSL-W and amphotericin B significantly decreased biofilm formation at 2, 4, and 6 days of culture. KSL-W also disrupted mature C. albicans biofilms. The effect of KSL-W on C. albicans growth, transition, and biofilm formation/disruption may thus occur through gene modulation, as the expression of various genes involved in C. albicans growth, transition and biofilm formation were all downregulated when C. albicans was treated with KSL-W. The effect was greater when C. albicans was cultured under hyphae-inducing conditions.ConclusionsThese data provide new insight into the efficacy of KSL-W against C. albicans and its potential use as an antifungal therapy.

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“…Because the expression of SAP genes varies depending on the type, phase, and site of infection (52, 62), we analyzed the expression of those genes in yeast cells upon contact with neutrophils, which either performed phagocytosis or exhibited a NETosis mode of action. It should be noted in this regard that SAP gene expression is also regulated during morphological transitions (63,64), which are often caused by physical contact with epithelial cells (65) or plasma proteins (60). The results confirm our supposition that a set of proteases including SAP2, SAP3, and SAP9 is induced in response to these two neutrophil actions.…”

Section: Figmentioning

confidence: 99%

Inactivation of the Antifungal and Immunomodulatory Properties of Human Cathelicidin LL-37 by Aspartic Proteases Produced by the Pathogenic Yeast Candida albicans

et al. 2015

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c Constant cross talk between Candida albicans yeast cells and their human host determines the outcome of fungal colonization and, eventually, the progress of infectious disease (candidiasis). An effective weapon used by C. albicans to cope with the host defense system is the release of 10 distinct secreted aspartic proteases (SAPs). Here, we validate a hypothesis that neutrophils and epithelial cells use the antimicrobial peptide LL-37 to inactivate C. albicans at sites of candidal infection and that C. albicans uses SAPs to effectively degrade LL-37. LL-37 is cleaved into multiple products by SAP1 to -4, SAP8, and SAP9, and this proteolytic processing is correlated with the gradual decrease in the antifungal activity of LL-37. Moreover, a major intermediate of LL-37 cleavage-the LL-25 peptide-is antifungal but devoid of the immunomodulatory properties of LL-37. In contrast to LL-37, LL-25 did not affect the generation of reactive oxygen species by neutrophils upon treatment with phorbol esters. Stimulating neutrophils with LL-25 (rather than LL-37) significantly decreased calcium flux and interleukin-8 production, resulting in lower chemotactic activity of the peptide against neutrophils, which may decrease the recruitment of neutrophils to infection foci. LL-25 also lost the function of LL-37 as an inhibitor of neutrophil apoptosis, thereby reducing the life span of these defense cells. This study indicates that C. albicans can effectively use aspartic proteases to destroy the antimicrobial and immunomodulatory properties of LL-37, thus enabling the pathogen to survive and propagate.A s a polymorphic opportunistic fungal pathogen, Candida albicans colonizes distinct niches in the human body such as the oral and vaginal cavities and the gut. In healthy individuals, C. albicans is controlled by the host immune system, epithelial barriers, and coexisting commensal microorganisms (1). However, under certain circumstances, C. albicans causes relatively easily curable superficial infections, as well as life-threatening deepseated and disseminated candidiases (2). The transition of C. albicans from a commensal to a pathogen depends mostly on the status of the host's immune system; therefore, the major risk factors for candidiasis include immunosuppressive therapy, indwelling vascular catheters, neutropenia, and prolonged treatment with broad-spectrum antibiotics (3). The pathogenic potential of C. albicans is determined by several factors, including molecules that mediate adhesion to and invasion of host cells, secreted hydrolases, polymorphisms, biofilm formation, and adaptation to stressful environmental conditions within the host organism (4).Neutrophils, which constitute the first line of host defense against microbial pathogens, are recruited to the infection site, where they rapidly respond with diverse antimicrobial mechanisms that demonstrate both intra-and extracellular processes such as phagocytosis and the degranulation and formation of neutrophil extracellular traps (NETs) (5). All of these processes inv...

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Farnesol, a Fungal Quorum-Sensing Molecule Triggers Candida Albicans Morphological Changes by Downregulating the Expression of Different Secreted Aspartyl Proteinase Genes

Cited by 40 publications

References 48 publications

Miconazole-Urea in a Buccal Film as a New Trend for Treatment of Resistant Mouth Fungal White Patches

Miconazole-Urea in a Buccal Film as a New Trend for Treatment of Resistant Mouth Fungal White Patches

C. albicansgrowth, transition, biofilm formation, and gene expression modulation by antimicrobial decapeptide KSL-W

Inactivation of the Antifungal and Immunomodulatory Properties of Human Cathelicidin LL-37 by Aspartic Proteases Produced by the Pathogenic Yeast Candida albicans

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