Phenotypic switching of<i>Candida tropicalis</i>is associated with cell damage in epithelial cells and virulence in<i>Galleria mellonella</i>model

Moralez, Alane Tatiana Pereira; Perini, Hugo Felix; Furlaneto-Maia, Luciana; Almeida, Ricardo Sérgio; Panagio, Luciano Aparecido; Furlaneto, Márcia Cristina

doi:10.1080/21505594.2016.1140297

Cited by 17 publications

(18 citation statements)

References 24 publications

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“…Macromorphology was examined following the reactivation of the irradiated yeast in 2 mL of Yeast Peptone Dextrose (YPD) liquid medium and incubated at 25 °C for 24 h. The inoculum was adjusted to a density of approximately 300 CFU/mL, uniformly seeded on plates containing YPD agar medium and maintained at room temperature for 96 h. The colonies were photographed under a digital microscope. The ultrastructure of the colony was analyzed by scanning electron microscopy (SEM) after lyophilization in accordance with Moralez et al [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

“…C. tropicalis from clinical isolates naturally exhibits highly diversified macromorphological variations known as phenotypic switching [ 12 , 13 ], an ability associated with cell damage in epithelial tissue. Although this virulence attribute has been observed in animal model [ 14 ], it is not known if the same occurs in humans. It is also not known if yeast exposed to radiation suffer changes in their putative virulence factors.…”

Section: Introductionmentioning

confidence: 99%

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Radiation used for head and neck cancer increases virulence in Candida tropicalis isolated from a cancer patient

et al. 2017

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BackgroundStudies have shown that radiation from radiotherapy increases the yeast colonization of patients. However it is not clear, if such radiation alters the yeast itself. The aim of the present study was therefore to report the direct impact of gamma radiation on Candida tropicalis. Methods C. tropicalis was obtained from a patient with a carcinoma, a suspension of this yeast containing 2.0 × 103 colony forming units per milliliter was prepared. It was submitted to gamma radiation dosage similar to that used in the treatment of head and neck cancer. After a cumulative dose of 7200 cGy some virulence attributes of C. tropicalis, including macro and micromorphological characteristics, adhesion and biofilm abilities, murine experimental infection and phagocytosis resistance were evaluated on irradiated and non-irradiated yeasts.ResultsAfter irradiation the colony morphology of the yeast was altered from a ring format to a smooth appearance in most colonies. Scanning electron microscopy revealed notable differences in the structures of both these colonies and the yeast cells, with the loss of pseudohyphae following irradiation and an increase in extracellular matrix production. The adherence and biofilm production of the yeast was greater following irradiation, both in terms of the number of yeasts and total biomass production on several abiotic surfaces and TR146 cells. The phagocytic index of the irradiated yeasts was not statistically different; however, the presence of cellular debris was detected in the kidneys of infected animals. Mice infected with irradiated yeasts developed an infection at the site of the yeast inoculation, although systemic infection was unchanged.ConclusionsOur findings show for the first time that C. tropicalis, one of the most important yeasts from colonization, which cause fatal candidemia in cancer patients, is affected by gamma irradiation, with changes to its virulence profile.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Radiation used for head and neck cancer increases virulence in Candida tropicalis isolated from a cancer patient

et al. 2017

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“…Concerning virulence fungal assays, studies have been reported using G. mellonella as an infection model for different Candida species (Scorzoni et al, 2013; Frenkel et al, 2016; Moralez et al, 2016), Cryptococcus spp. (Benaducci et al, 2016), Sporothrix schenckii (Clavijo-Giraldo et al, 2016), Paracoccidioides spp.…”

Section: Alternative Animal Models To Study Fungal Virulence and Antimentioning

confidence: 99%

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

et al. 2017

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The high rates of morbidity and mortality caused by fungal infections are associated with the current limited antifungal arsenal and the high toxicity of the compounds. Additionally, identifying novel drug targets is challenging because there are many similarities between fungal and human cells. The most common antifungal targets include fungal RNA synthesis and cell wall and membrane components, though new antifungal targets are being investigated. Nonetheless, fungi have developed resistance mechanisms, such as overexpression of eﬄux pump proteins and biofilm formation, emphasizing the importance of understanding these mechanisms. To address these problems, different approaches to preventing and treating fungal diseases are described in this review, with a focus on the resistance mechanisms of fungi, with the goal of developing efficient strategies to overcoming and preventing resistance as well as new advances in antifungal therapy. Due to the limited antifungal arsenal, researchers have sought to improve treatment via different approaches, and the synergistic effect obtained by the combination of antifungals contributes to reducing toxicity and could be an alternative for treatment. Another important issue is the development of new formulations for antifungal agents, and interest in nanoparticles as new types of carriers of antifungal drugs has increased. In addition, modifications to the chemical structures of traditional antifungals have improved their activity and pharmacokinetic parameters. Moreover, a different approach to preventing and treating fungal diseases is immunotherapy, which involves different mechanisms, such as vaccines, activation of the immune response and inducing the production of host antimicrobial molecules. Finally, the use of a mini-host has been encouraging for in vivo testing because these animal models demonstrate a good correlation with the mammalian model; they also increase the speediness of as well as facilitate the preliminary testing of new antifungal agents. In general, many years are required from discovery of a new antifungal to clinical use. However, the development of new antifungal strategies will reduce the therapeutic time and/or increase the quality of life of patients.

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“…Galleria mellonella models have become invaluable to study cellular and humoral immune responses against pathogens [31–33], epigenetic influences on the evolution of virulence [32,34,35], and for development and testing antimicrobials [36–39]. It is relevant to add that the complete genomes of P. destructans and G. mellonella have become available recently [40,41].…”

Section: Resultsmentioning

confidence: 99%

Galleria mellonella experimental model for bat fungal pathogen Pseudogymnoascus destructans and human fungal pathogen Pseudogymnoascus pannorum

et al. 2018

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Laboratory investigations of the pathogenesis of Pseudogymnoascus destructans, the fungal causal agent of bat White Nose Syndrome (WNS), presents unique challenges due to its growth requirements (4°-15°C) and a lack of infectivity in the current disease models. Pseudogymnoascus pannorum is the nearest fungal relative of P. destructans with wider psychrophilic – physiological growth range, and ability to cause rare skin infections in humans. Our broad objectives are to create the molecular toolkit for comparative study of P. destructans and P. pannorum pathogenesis. Towards these goals, we report the successful development of an invertebrate model in the greater wax moth Galleria mellonella. Both P. destructans and P. pannorum caused fatal disease in G. mellonella and elicited immune responses and histopathological changes consistent with the experimental disease.

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Phenotypic switching ofCandida tropicalisis associated with cell damage in epithelial cells and virulence inGalleria mellonellamodel

Abstract: (2016) Phenotypic switching of Candida tropicalis is associated with cell damage in epithelial cells and virulence in Galleriamellonella model, Virulence, 7:4,[379][380][381][382][383][384][385][386]

Cited by 17 publications

References 24 publications

Radiation used for head and neck cancer increases virulence in Candida tropicalis isolated from a cancer patient

Radiation used for head and neck cancer increases virulence in Candida tropicalis isolated from a cancer patient

Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

Galleria mellonella experimental model for bat fungal pathogen Pseudogymnoascus destructans and human fungal pathogen Pseudogymnoascus pannorum

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