Cyclooxygenase inhibitors reduce biofilm formation and yeast-hypha conversion of fluconazole resistant Candida albicans

Abdelmegeed, Eman Salama; Shaaban, Mona I.

doi:10.1007/s12275-013-3052-6

Cited by 33 publications

(32 citation statements)

References 41 publications

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“…However, they appear to be important metabolites, since we found that cyclooxygenase inhibitors prevented hyphal growth and zoospore germination of S. parasitica, even in the absence of a clear COX homologue. This apparent paradox has also been reported in true fungi, such as Candida spp., where although no COX homologue is known, COX inhibitors prevent PGE 2 production, the yeast-hypha transition, yeast and hyphae growth, and biofilm formation (23,(39)(40)(41)(42). The exact role of these lipids in oomycete biology needs to be further addressed, as off-target effects of aspirin and indomethacin cannot be ruled out at this point.…”

Section: Discussionmentioning

confidence: 99%

Role of Pathogen-Derived Cell Wall Carbohydrates and Prostaglandin E ₂ in Immune Response and Suppression of Fish Immunity by the Oomycete Saprolegnia parasitica

et al. 2014

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e Saprolegnia parasitica is a freshwater oomycete that is capable of infecting several species of fin fish. Saprolegniosis, the disease caused by this microbe, has a substantial impact on Atlantic salmon aquaculture. No sustainable treatment against saprolegniosis is available, and little is known regarding the host response. In this study, we examined the immune response of Atlantic salmon to S. parasitica infection and to its cell wall carbohydrates. Saprolegnia triggers a strong inflammatory response in its host (i.e., induction of interleukin-1␤ 1 [IL-1␤ 1 ], IL-6, and tumor necrosis factor alpha), while severely suppressing the expression of genes associated with adaptive immunity in fish, through downregulation of T-helper cell cytokines, antigen presentation machinery, and immunoglobulins. Oomycete cell wall carbohydrates were recognized by fish leukocytes, triggering upregulation of genes involved in the inflammatory response, similar to what is observed during infection. Our data suggest that S. parasitica is capable of producing prostaglanding E 2 (PGE 2 ) in vitro, a metabolite not previously shown to be produced by oomycetes, and two proteins with homology to vertebrate enzymes known to play a role in prostaglandin biosynthesis have been identified in the oomycete genome. Exogenous PGE 2 was shown to increase the inflammatory response in fish leukocytes incubated with cell wall carbohydrates while suppressing genes involved in cellular immunity (gamma interferon [IFN-␥] and the IFN-␥-inducible protein [␥-IP]). Inhibition of S. parasitica zoospore germination and mycelial growth by two cyclooxygenase inhibitors (aspirin and indomethacin) also suggests that prostaglandins may be involved in oomycete development.

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Section: Discussionmentioning

confidence: 99%

Role of Pathogen-Derived Cell Wall Carbohydrates and Prostaglandin E ₂ in Immune Response and Suppression of Fish Immunity by the Oomycete Saprolegnia parasitica

et al. 2014

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“…Fluconazole-resistant C. albicans is responsible for most prevalent nosocomial fungal infections and has resulted in many clinical treatment failures in immunocompromised patients, leading to the search for novel antifungal agents urgent (Schulz et al 2011;Abdelmegeed and Shaaban 2013). KAE was considered a promising candidate to enhance the efficacy of traditional antifungal drug (such as FLC).…”

Section: Discussionmentioning

confidence: 99%

The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans

Shao

Zhang

Wang

et al. 2015

Pharmaceutical Biology

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Context: Fungal infections caused by fluconazole-resistant Candida albicans are an intractable clinical problem, calling for new efficient antifungal drugs. Kaempferol, an active flavonoid, has been considered a potential candidate against Candida species. Objective: This work investigates the resistance reversion of kaempferol in fluconazole-resistant C. albicans and the underlying mechanism. Materials and methods: The antifungal activities of fluconazole and/or kaempferol were assessed by a series of standard procedures including broth microdilution method, checkerboard assay and time-kill (T-K) test in nine clinical strains as well as a standard reference isolate of C. albicans. Subsequently, the morphological changes, the efflux of rhodamine 6G, and the expressions of CDR 1, CDR 2, and MDR 1 were analysed by scanning electron microscope (SEM), inverted fluorescence microscope and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in C. albicans z2003.Results: For all the tested C. albicans strains, the minimum inhibitory concentrations (MICs) of fluconazole and kaempferol ranged 0.25-32 and 128-256 mg/mL with a range of fractional inhibitory concentration index of 0.257-0.531. In C. albicans z2003, the expression of both CDR 1 and CDR 2 were decreased after exposure to kaempferol alone with negligible rhodamine 6G accumulation, while the expression of CDR 1, CDR 2 and MDR 1 were all decreased when fluconazole and kaempferol were used concomitantly with notable fluorescence of rhodamine 6G observed. Discussion and conclusion: Kaempferol-induced reversion in fluconazole-resistant C. albicans might be likely due to the suppression of the expression of CDR1, CDR2 and MDR1.ARTICLE HISTORY

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“…It can significantly reduce biofilm synthesis in fluconazole resistant C. albicans clinical isolates at a concentration of 1 mg/ml and eliminate biofilm formation at a concentration of 5 mg/ml (Abdelmegeed and Shaaban, 2013). Aspirin also has significant effects on the viability of C. albicans biofilm cells.…”

Section: Cyclooxygenasementioning

confidence: 99%

Potential Antifungal Targets against a Candida Biofilm Based on an Enzyme in the Arachidonic Acid Cascade—A Review

Liu

Wang

et al. 2016

Front. Microbiol.

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Candida is an important opportunistic fungal pathogen, especially in biofilm associated infections. The formation of a Candida biofilm can decrease Candida sensitivity to antifungal drugs and cause drug resistance. Although many effective antifungal drugs are available, their applications are limited due to their high toxicity and cost. Seeking new antifungal agents that are effective against biofilm-associated infection is an urgent need. Many research efforts are underway, and some progress has been made in this field. It has been shown that the arachidonic acid cascade plays an important role in fungal morphogenesis and pathogenicity. Notably, prostaglandin E2 (PGE2) can promote the formation of a Candida biofilm. Recently, the inhibition of PGE2 has received much attention. Studies have shown that cyclooxygenase (COX) inhibitors, such as aspirin, ibuprofen, and indomethacin, combined with fluconazole can significantly reduce Candida adhesion and biofilm development and increase fluconazole susceptibility; the MIC of fluconazole can be decrease from 64 to 2 μg/ml when used in combination with ibuprofen. In addition, in vivo studies have also confirmed the antifungal activities of these inhibitors. In this article, we mainly review the relationship between PGE2 and Candida biofilm, summarize the antifungal activities of COX inhibitors and analyze the possible antifungal activity of microsomal prostaglandin E synthase-1 (MPGES-1) inhibitors; additionally, other factors that influence PGE2 production are also discussed. Hopefully this review can disclose potential antifungal targets based on the arachidonic acid cascade and provide a prevailing strategy to alleviate Candida albicans biofilm formation.

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Cyclooxygenase inhibitors reduce biofilm formation and yeast-hypha conversion of fluconazole resistant Candida albicans

Cited by 33 publications

References 41 publications

Role of Pathogen-Derived Cell Wall Carbohydrates and Prostaglandin E ₂ in Immune Response and Suppression of Fish Immunity by the Oomycete Saprolegnia parasitica

Role of Pathogen-Derived Cell Wall Carbohydrates and Prostaglandin E ₂ in Immune Response and Suppression of Fish Immunity by the Oomycete Saprolegnia parasitica

The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans

Potential Antifungal Targets against a Candida Biofilm Based on an Enzyme in the Arachidonic Acid Cascade—A Review

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Cyclooxygenase inhibitors reduce biofilm formation and yeast-hypha conversion of fluconazole resistant Candida albicans

Cited by 33 publications

References 41 publications

Role of Pathogen-Derived Cell Wall Carbohydrates and Prostaglandin E 2 in Immune Response and Suppression of Fish Immunity by the Oomycete Saprolegnia parasitica

Role of Pathogen-Derived Cell Wall Carbohydrates and Prostaglandin E 2 in Immune Response and Suppression of Fish Immunity by the Oomycete Saprolegnia parasitica

The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans

Potential Antifungal Targets against a Candida Biofilm Based on an Enzyme in the Arachidonic Acid Cascade—A Review

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Role of Pathogen-Derived Cell Wall Carbohydrates and Prostaglandin E ₂ in Immune Response and Suppression of Fish Immunity by the Oomycete Saprolegnia parasitica

Role of Pathogen-Derived Cell Wall Carbohydrates and Prostaglandin E ₂ in Immune Response and Suppression of Fish Immunity by the Oomycete Saprolegnia parasitica