A novel ex vivo skin model to study the susceptibility of the dermatophyte Trichophyton rubrum to photodynamic treatment in different growth phases

Smijs, Threes G. M.; Bouwstra, Joke A.; Schuitmaker, Hans J.; Talebi, Mojgan; Pavel, S.

doi:10.1093/jac/dkl490

Cited by 62 publications

(49 citation statements)

References 16 publications

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“…In line with this assumption, previous studies of reconstituted human epithelia infected with C. albi- cans revealed that supplementation of the model with polymorphonuclear leukocytes strongly impaired tissue invasion by this pathogenic yeast (22). In the past, various in vitro models using reconstituted epidermis or skin explants have been established and were also proven successful for the analysis of dermatophytosis (1,2,5,7,19,20,24,26). Nevertheless, the commercially available RHE model, which was employed in the present study for the analysis of A. benhamiae mutants, may further advance the research of dermatophytosis and the identification of basic virulence attributes of dermatophytes.…”

Section: Discussionmentioning

confidence: 82%

Targeted Gene Deletion and In Vivo Analysis of Putative Virulence Gene Function in the Pathogenic Dermatophyte Arthroderma benhamiae

et al. 2011

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Dermatophytes cause the majority of superficial mycoses in humans and animals. However, little is known about the pathogenicity of this specialized group of filamentous fungi, for which molecular research has been limited thus far. During experimental infection of guinea pigs by the human pathogenic dermatophyte Arthroderma benhamiae, we recently detected the activation of the fungal gene encoding malate synthase AcuE, a key enzyme of the glyoxylate cycle. By the establishment of the first genetic system for A. benhamiae, specific ⌬acuE mutants were constructed in a wild-type strain and, in addition, in a derivative in which we inactivated the nonhomologous end-joining pathway by deletion of the A. benhamiae KU70 gene. The absence of AbenKU70 resulted in an increased frequency of the targeted insertion of linear DNA by homologous recombination, without notably altering the monitored in vitro growth abilities of the fungus or its virulence in a guinea pig infection model. Phenotypic analyses of ⌬acuE mutants and complemented strains depicted that malate synthase is required for the growth of A. benhamiae on lipids, major constituents of the skin. However, mutant analysis did not reveal a pathogenic role of the A. benhamiae enzyme in guinea pig dermatophytosis or during epidermal invasion of the fungus in an in vitro model of reconstituted human epidermis. The presented efficient system for targeted genetic manipulation in A. benhamiae, paired with the analyzed infection models, will advance the functional characterization of putative virulence determinants in medically important dermatophytes.Dermatophytes represent a group of specialized filamentous fungi which account for the majority of superficial fungal infections. Millions of so-called dermatophytoses, which in many cases are long lasting and difficult to eradicate, are recorded for humans and animals every year (29). As a peculiarity, dermatophytes specifically infect keratinized host structures, such as stratum corneum, hair, and nails. At the molecular level, however, little is known of the nature of the pathogenicity mechanisms in dermatophytes (17,30). This drawback might be related to the fact that these fungi, which grow comparatively slowly under laboratory conditions, have so far not intensively been studied genetically, in contrast to other medically important fungi, such as Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. Full genome sequence information for dermatophytes have been available since only very recently (http://www.broadinstitute.org /annotation/genome/dermatophyte_comparative/MultiHome .html), and genetic tools have hardly been established. As a consequence, in dermatophyte species only a few genes have to date been analyzed by targeted inactivation, i.e., pacC and MDR2 in Trichophyton rubrum (8, 9), Ku80, areA, and Trim4 in Trichophyton mentagrophytes (Arthroderma vanbreuseghemii) (32), and areA in Microsporum canis (31). Specifically constructed dermatophyte mutants have, to our knowledge, not yet been tested ...

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Section: Discussionmentioning

confidence: 82%

Targeted Gene Deletion and In Vivo Analysis of Putative Virulence Gene Function in the Pathogenic Dermatophyte Arthroderma benhamiae

et al. 2011

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“…at room temperature (RT). Microconidia suspensions were prepared as described previously and stored in liquid nitrogen for no longer than 6 months [9,10]. Counting the number of colony forming units (cfu) on malt extract agar (MEA, Oxoid, Hampshire, UK) was used as a viability check.…”

Section: Chemicalsmentioning

confidence: 99%

Mechanical Properties of Healthy and ex vivo Onychomycosis Nails and the Influence of a Porphyrin-propylene Glycol Antifungal Formulation

Hosseinzoi

Galli

Incrocci

et al. 2016

BJAST

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Aims: To investigate nail penetration enhancing effectiveness of a novel drug formulation and ingredients, 40% propylene glycol (PG) and 40 µM multifunctional photosensitizer (MFPS). Proposed formulation was proven effective in photodynamic treatment (PDT) of ex vivo fungal infections of human nails (onychomycoses) and indirectly also to weaken nail's strength. Study Design: To directly proof the effect of the novel formulation on nail's hardness Atomic Force Microscopy (AFM) was employed to measure small-distance forces. Based on indentations Young's moduli of healthy and ex vivo onychomycosis nails were calculated before and after treatment with the novel formulation. Changes in young's modulus can be related to changes in nail's strength and thus formulation effectiveness. Additionally, AFM imaging was employed to study topographical / roughness changes resulting from the treatments to both nail types. Trichophyton mentagrophytes, representative for clinical onychomycosis, was chosen to induce nail infections.

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“…Hence, tinea capitis, tinea barbae, tinea corporis, tinea manum, tinea cruris, tinea pedis, and tinea unguium refer to dermatophytic infections of the scalp, beard, body, hands, inguinal folds, feet, and nails, respectively. Together, these infections affect at least 10% of the US population at any given time [1,2].…”

Section: Introductionmentioning

confidence: 99%

Dermatophytes

Dahdah

Scher²

2008

Curr Fungal Infect Rep

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A novel ex vivo skin model to study the susceptibility of the dermatophyte Trichophyton rubrum to photodynamic treatment in different growth phases

Cited by 62 publications

References 16 publications

Targeted Gene Deletion and In Vivo Analysis of Putative Virulence Gene Function in the Pathogenic Dermatophyte Arthroderma benhamiae

Targeted Gene Deletion and In Vivo Analysis of Putative Virulence Gene Function in the Pathogenic Dermatophyte Arthroderma benhamiae

Mechanical Properties of Healthy and ex vivo Onychomycosis Nails and the Influence of a Porphyrin-propylene Glycol Antifungal Formulation

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