Antimicrobial decapeptide KSL-W attenuates Candida albicans virulence by modulating its effects on Toll-like receptor, human β-defensin, and cytokine expression by engineered human oral mucosa

Semlali, Abdelhabib; Leung, Kai P.; Curt, Sèverine; Rouabhia, Mahmoud

doi:10.1016/j.peptides.2011.01.020

Cited by 39 publications

(33 citation statements)

References 47 publications

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“…As described by Semlali et al,32,33 RNA (1 μg of each sample) was reverse-transcribed into cDNA using a high-capacity cDNA reverse transcription kit (Applied Biosystems, Warrington, PA, USA). The preparation conditions of the cDNA templates for polymerase chain reaction (PCR) were as follows: 10 minutes at 25°C, 2 hours at 37°C, and 5 minutes at 85°C.…”

Section: Methodsmentioning

confidence: 99%

Association between <em>TLR-9</em> polymorphisms and colon cancer susceptibility in Saudi Arabian female patients

Semlali

Parine

Amri

et al. 2016

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ObjectiveThe authors aimed to explore the relationship between the expression/polymorphisms of TLR-9 and susceptibility to colon cancer development in the Saudi Arabian population.MethodsIn total, blood samples from 115 patients with colon cancer and 102 participants without colon cancer were analyzed in this study. Three single-nucleotide polymorphisms (SNPs) were selected from the TLR-9 gene, including two sites within the TLR-9 gene’s promoter region (rs352144 and rs187084) and one site in a TLR-9 intron region (rs5743839). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models after adjusting for age, gender, and tumor localization. To investigate the differential expression of TLR-9 in colon cancer, TLR-9 expression was evaluated using quantitative real-time reverse transcription polymerase chain reaction on 40 matched normal and colon tissues.ResultsThe authors found that TLR-9 expression was decreased in colon cancer tissues as compared with that in normal tissues. Moreover, significant associations between the TLR-9 rs187084 SNP and colon cancer risk were observed in female patients only. In rs187084, the T allele had a significantly lower frequency (2.8 times) in female cancer patients than in controls (0.27 vs 0.41). The TLR-9 rs352139 and rs352144 SNPs were significantly associated with colon cancer development when the tumor was located in the rectal area.ConclusionThe findings support the hypothesis that TLR-9 has an anticancer role in colon cancer development. Furthermore, genetic variation may influence colon cancer development, and SNPs in TLR-9 could serve as biomarkers for decision making in the treatment of females with rectal cancer.

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Section: Methodsmentioning

confidence: 99%

Association between <em>TLR-9</em> polymorphisms and colon cancer susceptibility in Saudi Arabian female patients

Semlali

Parine

Amri

et al. 2016

OTT

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“…The conditions for the preparation of the cDNA templates for PCR analysis were 5 min at 25°C, 1 h at 42°C, and 5 min at 85°C. Quantitative PCR (qPCR) was carried out as previously described [36]. The quantity of mRNA transcripts was measured with the Bio-Rad CFX96 real-time PCR detection system.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, combined with sub-inhibitory concentrations of benzalkonium chloride, a known cationic surface-active agent [35], KSL was shown to significantly promote bacterial biofilm susceptibility. We also recently demonstrated that KSL-W had a selective effect on C. albicans growth, while exhibiting no toxic effect on epithelial cells [36]. …”

Section: Introductionmentioning

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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“…This ultimately dictates the outcome of pathogenic dissemination [24], [25]. During the development of candidiasis, numerous types of immune cells including neutrophils, tissue macrophages, monocytes and dendritic cells interact with the fungus [26]–[28]. Most in vitro studies used a single cell type to infection with C. albicans [29], [30].…”

Section: Introductionmentioning

confidence: 99%

First Human Model of In Vitro Candida albicans Persistence within Granuloma for the Reliable Study of Host-Fungi Interactions

et al. 2012

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BackgoundThe balance between human innate immune system and Candida albicans virulence signaling mechanisms ultimately dictates the outcome of fungal invasiveness and its pathology. To better understand the pathophysiology and to identify fungal virulence-associated factors in the context of persistence in humans, complex models are indispensable. Although fungal virulence factors have been extensively studied in vitro and in vivo using different immune cell subsets and cell lines, it is unclear how C. albicans survives inside complex tissue granulomas.Methodology/Principal FindingWe developed an original model of in vitro human granuloma, reproducing the natural granulomatous response to C. albicans. Persistent granulomas were obtained when the ratio of phagocytes to fungi was high. This in vitro fungal granuloma mimics natural granulomas, with infected macrophages surrounded by helper and cytotoxic T lymphocytes. A small proportion of granulomas exhibited C. albicans hyphae. Histological and time-lapse analysis showed that C. albicans blastoconidia were located within the granulomas before hyphae formation. Using staining techniques, fungal load calculations, as well as confocal and scanning electron microscopy, we describe the kinetics of fungal granuloma formation. We provide the first direct evidence that C. albicans are not eliminated by immunocompetent cells inside in vitro human granulomas. In fact, after an initial candicidal period, the remaining yeast proliferate and persist under very complex immune responses.Conclusions/SignificanceUsing an original in vitro model of human fungal granuloma, we herein present the evidence that C. albicans persist and grow into immunocompetent granulomatous structures. These results will guide us towards a better understanding of fungal invasiveness and, henceforth, will also help in the development of better strategies for its control in human physiological conditions.

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Antimicrobial decapeptide KSL-W attenuates Candida albicans virulence by modulating its effects on Toll-like receptor, human β-defensin, and cytokine expression by engineered human oral mucosa

Cited by 39 publications

References 47 publications

Association between <em>TLR-9</em> polymorphisms and colon cancer susceptibility in Saudi Arabian female patients

Association between <em>TLR-9</em> polymorphisms and colon cancer susceptibility in Saudi Arabian female patients

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

First Human Model of In Vitro Candida albicans Persistence within Granuloma for the Reliable Study of Host-Fungi Interactions

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