Secreted subtilisins of Microsporum canis are involved in adherence of arthroconidia to feline corneocytes

Baldo, Aline; Tabart, Jessica; Vermout, S.; Mathy, Anne; Collard, Alfred; Losson, Bertrand; Mignon, Bernard

doi:10.1099/jmm.0.47827-0

Cited by 50 publications

(52 citation statements)

References 25 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: 69%

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: 69%

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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“…Nevertheless, it is clear that an extracellular pH shift is not required for the inhibitory action of UDA on the H6 strain grown on Tween 20 or keratin cultures. Indeed, it is possible that a contact sensing response for fungal growth on Tween 20 or keratin avoids the inhibitory action of UDA (Baldo et al 2008;Kumamoto 2008).…”

Section: Discussionmentioning

confidence: 99%

In vitro susceptibility to antimycotic drug undecanoic acid, a medium-chain fatty acid, is nutrient-dependent in the dermatophyte Trichophyton rubrum

Peres

Cursino‐Santos

Rossi

et al. 2010

World J Microbiol Biotechnol

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The antimycotic activity of fatty acids has long been known, and their presence in human skin and sweat appears to protect the host against superficial mycoses. Undecanoic acid is a medium-chain fatty acid that has been used in the treatment of dermatophytoses in humans. In this study, we selected one Trichophyton rubrum undecanoic acid-resistant strain that showed a marked reduction in its capacity to grow on human nail fragments, which correlated with the reduced activity of secreted keratinolytic proteases. Moreover, the susceptibility of T. rubrum to undecanoic acid is also dependent on the carbon source utilized by both control and resistant strains. The growth of the control strain was strongly inhibited by undecanoic acid in Sabouraud medium or in cultures supplemented with low-fat milk, whereas it was ineffective when the cultures were supplemented with Tween 20 or keratin as the carbon source, suggesting that nutrient conditions are crucial in establishing a susceptibility to antifungal drugs, which is helpful for the isolation and characterization of resistant strains, and in the screening for new antifungal drugs.

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“…In M. canis, adherence to feline corneocytes was previously found to be reduced by the use of chymostatin, a serine protease inhibitor and by the use of a mixture of two monoclonal antibodies against Sub3. 24 In the pathogenic bacteria Porphyromonas gingivalis and Streptococcus pneumoniae, a membrane-associated dipeptidyl peptidase IV and a surface-associated serine protease named choline-binding protein G, respectively, are involved in adherence. 25,26 Similarly, in the yeast Candida albicans, a family of 10 secreted proteases (Saps) is involved in the adherence and invasion of skin and mucosal surfaces.…”

Section: Discussionmentioning

confidence: 99%

Secreted subtilisin Sub3 from Microsporum canis is required for adherence to but not for invasion of the epidermis

Baldo¹,

Mathy²,

Tabart³

et al. 2009

British Journal of Dermatology

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Secreted subtilisins of Microsporum canis are involved in adherence of arthroconidia to feline corneocytes

Cited by 50 publications

References 25 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

In vitro susceptibility to antimycotic drug undecanoic acid, a medium-chain fatty acid, is nutrient-dependent in the dermatophyte Trichophyton rubrum

Secreted subtilisin Sub3 from Microsporum canis is required for adherence to but not for invasion of the epidermis

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