Dataset Information

Markers for host-induced gene expression in Trichophyton dermatophytosis.

ABSTRACT: Dermatophytes are adapted to infect keratinized tissues by their ability to utilize keratin as a nutrient source. Although there have been numerous reports that dermatophytes like Trichophyton sp. secrete proteolytic enzymes, virtually nothing is known about the patterns of gene expression in the host or even when the organisms are cultured on protein substrates in the absence of a host. We characterized the expression of an aminopeptidase gene, the Trichophyton mentagrophytes homolog of the Trichophyton rubrum Tri r 4 gene. The T. rubrum gene was originally isolated based on the ability of the protein encoded by it to induce immediate and delayed-type hypersensitivity in skin tests. T. mentagrophytes Tri m 4 is closely related to Tri r 4 (almost 94% identity at the protein level). Tri m 4 resembles other protease-encoding genes thought to be virulence factors (for example, DPP V of Aspergillus fumigatus). The Tri m 4 protein was detected immunochemically both in fungal extracts and in the culture medium. Expression of the Tri m 4 gene was induced severalfold when T. mentagrophytes was grown on keratin and elastin. Ex vivo, strong induction was observed after culture on blood plasma, but the use of homogenized skin did not result in a significant increase in Tri m 4 transcript levels. In order to identify additional genes encoding putative virulence factors, differential cDNA screening was performed. By this method, a fungal thioredoxin and a cellulase homolog were identified, and both genes were found to be strongly induced by skin extracellular matrix proteins. Induction by superficial (keratin) and deep (elastin) skin elements suggests that the products of these genes may be important in both superficial and deep dermatophytosis, and models for their function are proposed. Upregulation of several newly identified T. mentagrophytes genes on protein substrates suggests that these genes encode proteins which are relevant to the dermatophyte-skin interaction.

SUBMITTER: Kaufman G

PROVIDER: S-EPMC1230929 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature

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Markers for host-induced gene expression in Trichophyton dermatophytosis.

Kaufman Gil G Berdicevsky Israela I Woodfolk Judith A JA Horwitz Benjamin A BA

Infection and immunity 20051001 10

Dermatophytes are adapted to infect keratinized tissues by their ability to utilize keratin as a nutrient source. Although there have been numerous reports that dermatophytes like Trichophyton sp. secrete proteolytic enzymes, virtually nothing is known about the patterns of gene expression in the host or even when the organisms are cultured on protein substrates in the absence of a host. We characterized the expression of an aminopeptidase gene, the Trichophyton mentagrophytes homolog of the Tri ...[more]

PMID: 16177334

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Project description:Trichophyton erinacei is a main cause of dermatophytosis in hedgehogs and is increasingly reported from human infections worldwide. This pathogen was originally described in the European hedgehog (Erinaceus europaeus) but is also frequently found in the African four-toed hedgehog (Atelerix albiventris), a popular pet animal worldwide. Little is known about the taxonomy and population genetics of this pathogen despite its increasing importance in clinical practice. Notably, whether there are different populations or even cryptic species associated with different hosts or geographic regions is not known. To answer these questions, we collected 161 isolates, performed phylogenetic and population-genetic analyses, determined mating-type, and characterised morphology and physiology. Multigene phylogeny and microsatellite analysis supported T. erinacei as a monophyletic species, in contrast to highly incongruent single-gene phylogenies. Two main subpopulations, one specific mainly to Atelerix and second to Erinaceus hosts, were identified inside T. erinacei, and slight differences in the size of microconidia and antifungal susceptibilities were observed among them. Although the process of speciation into two lineages is ongoing in T. erinacei, there is still gene flow between these populations. Thus, we present T. erinacei as a single species, with notable intraspecies variability in genotype and phenotype. The data from wild hedgehogs indicated that sexual reproduction in T. erinacei and de novo infection of hedgehogs from soil are probably rare events and that clonal horizontal spread strongly dominates. The molecular typing approach used in this study represents a suitable tool for further epidemiological surveillance of this emerging pathogen in both animals and humans. The results of this study also highlighted the need to use a multigene phylogeny ideally in combination with other independent molecular markers to understand the species boundaries of dermatophytes. Citation: Čmoková A, Kolařík M, Guillot J, et al. 2022. Host-driven subspeciation in the hedgehog fungus, Trichophyton erinacei, an emerging cause of human dermatophytosis. Persoonia 48: 203-218. https://doi.org/10.3767/persoonia.2022.48.06.

Project description:Dermatophytes are agents of typically benign superficial infections. However, an increasing number of severe infections in immunocompromised hosts has been reported. We aimed to understand the factors underlying the existence of a cohort of patients presenting with chronic widespread dermatophytosis (CWD) due to Trichophyton rubrum, but with no signs of immunodeficiency. Their disease is usually recurrent and difficult to manage. Fourteen patients meeting the following criteria for CWD were studied: T. rubrum culture-proven skin lesions of ?10 cm in at least one dimension; the involvement of at least three non-contiguous localizations of >1 year's duration; and no predisposing conditions. For comparison, we also studied 13 acute Tinea pedis patients. Macrophages and neutrophils were isolated and tested for T. rubrum conidia phagocytic and killing activity. H2O2, NO, and pro- and anti-inflammatory cytokine release were measured. All experiments were run with age- and sex-matched healthy donors' cells in parallel. CWD patients' macrophages and neutrophils presented with reduced T. rubrum-phagocytic and killing abilities, and reduced H2O2 and NO release when compared with those of healthy donors. CWD patients' macrophages secreted lower levels of the proinflammatory cytokines interleukin (IL)-1?, IL-6, IL-8, and tumor necrosis factor (TNF)-?, but enhanced levels of the anti-inflammatory cytokine IL-10. Neutrophil secretion closely followed this unbalanced pattern. In contrast, responses to the positive controls zymosan, lipopolysaccharide, and phorbol myristate acetate were comparable with those of healthy donors. The same experiments were performed with macrophages and neutrophils from the acute Tinea pedis patients and showed no differences when compared with the matched healthy donors. Patients with CWD have a T. rubrum-related functional deficiency of phagocytes and may represent a distinct clinical entity in the complex spectrum of the Trichophyton-host interaction.

Dataset Information

Markers for host-induced gene expression in Trichophyton dermatophytosis.

Publications

Markers for host-induced gene expression in Trichophyton dermatophytosis.

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