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

Baldo, Aline; Mathy, Anne; Tabart, Jessica; Camponova, Paméla; Vermout, S.; Massart, L; Maréchal, Françoise; Galleni, Moreno; Mignon, Bernard

doi:10.1111/j.1365-2133.2009.09608.x

Cited by 63 publications

(59 citation statements)

References 40 publications

(55 reference statements)

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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: 70%

“…Animal infection was monitored twice weekly for 7 weeks by two independent examiners using clinical criteria, as previously described (1,3). The examiners remained the same for the duration of the experiment.…”

Section: Methodsmentioning

confidence: 99%

“…During the entire study, animals were housed separately. Infection was performed essentially as shown previously (1,25). In brief, animals were anesthetized by intraperitoneal injection of medetomidine and ketamine.…”

Section: Methodsmentioning

confidence: 99%

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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: 70%

Section: Methodsmentioning

confidence: 99%

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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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“…This model has been useful for zoophiles [33, 52–54] but does not provide an accurate infection model for most anthropophilic species [4]. A murine model has been useful for studying the immune response to dermatophytes [55, 56], but again the mice only develop disease in response to infection by zoophiles.…”

Section: Testing the Role Of Putative Virulence Factorsmentioning

confidence: 99%

Dermatophyte Virulence Factors: Identifying and Analyzing Genes That May Contribute to Chronic or Acute Skin Infections

Achterman

White

2012

International Journal of Microbiology

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Dermatophytes are prevalent causes of cutaneous mycoses and, unlike many other fungal pathogens, are able to cause disease in immunocompetent individuals. They infect keratinized tissue such as skin, hair, and nails, resulting in tinea infections, including ringworm. Little is known about the molecular mechanisms that underlie the ability of these organisms to establish and maintain infection. The recent availability of genome sequence information and improved genetic manipulation have enabled researchers to begin to identify and study the role of virulence factors of dermatophytes. This paper will summarize our current understanding of dermatophyte virulence factors and discuss future directions for identifying and testing virulence factors.

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“…In cats, several attempts have been made to develop vaccines using characterized antigens from M. canis. The protective efficacy of a crude exo-antigen and two recombinant proteases, the subtilisin rSub3, a fungal endopeptidase involved in adherence of M. canis to human and animal epidermis (Baldo et al, 2010;Bagut et al, 2012), and the metalloprotease rMep3 have been tested in experimentally induced M. canis infections in guinea pig with inconclusive results (Descamps et al, 2003;Vermout et al, 2004). The development of safe and effective vaccines requires the use of both appropriate antigens and adjuvants.…”

mentioning

confidence: 99%

Assessment of immunogenicity and protective efficacy of Microsporum canis secreted components coupled to monophosphoryl lipid-A adjuvant in a vaccine study using guinea pigs

Cambier

Băguţ

Heinen

et al. 2015

Veterinary Microbiology

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Microsporum canis is the most common dermatophyte in pets and is of zoonotic importance but currently there is no effective vaccine available to prevent dermatophytosis. The aim of this work was to assess the immunogenicity and protective efficacy of secreted components (SC) from M. canis adjuvanted with the monophosphoryl lipid-A (MPLA), in a vaccine study using the guinea pig as an experimental model. Animals were vaccinated with either the SC adjuvanted with the MPLA, the MPLA adjuvant alone or PBS three times at two-week intervals, until 42 days prior to M. canis infection. A blind evaluation of dermatophytosis symptoms development and fungal persistence in skin was monitored weekly. The antibody response towards the SC and the levels of Interferon (IFN)γ and Interleukin-4 expressed in peripheral blood mononuclear cells were assessed along or at the end of the study period respectively. The animals that received MPLA had a significantly lower clinical score than those inoculated with PBS. However, no significant difference was observed between the guinea pigs vaccinated with the SC adjuvanted with the MPLA and those having received MPLA alone. The results also showed that vaccination induced a strong antibody response towards the SC and an increase in IFNγ mRNA level. Our results show that the MPLA adjuvant used in this vaccine study can induce per se a partial protection against a M. canis infection. Although they induce a delayed-type hypersensitivity reaction in guinea pigs, the SC do not confer a protection under the present experimental conditions.

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

Abstract: RNA interference is a useful tool to evaluate pathogenic mechanisms of M. canis. For the first time, a role in pathogenicity could be attributed to a protease of a dermatophyte, namely Sub3 from M. canis, which is required for adherence to but not for invasion of the epidermis.

Cited by 63 publications

References 40 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

Dermatophyte Virulence Factors: Identifying and Analyzing Genes That May Contribute to Chronic or Acute Skin Infections

Assessment of immunogenicity and protective efficacy of Microsporum canis secreted components coupled to monophosphoryl lipid-A adjuvant in a vaccine study using guinea pigs

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