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LysM1 and LysM2 bind to glycoproteins from human skin lysates. Proteins from human skin lysates were subjected to SDS PAGE, and the ability of MBP::LysM1, MBP::LysM1 domains 2 and 3, MBP::LysM2, and MBP to bind to these proteins was determined in a Western blot type assay with antibody directed against MBP. Lane 1 contains molecular weight markers. Lanes 2 through 6 contain human skin lysate (10 ugr). The lysate in lane 3 was treated with PNGase F prior to being subjected to electrophoresis. Lanes 2 and 3 were probed with MBP::LysM1. Lane 4 was probed with MBP::LysM1 domains 2 and 3. Lane 5 was probed with MBP::LysM2. Lane 6 was probed with MBP as a control. Note that LysM1, LysM1 domains 2 and 3, and LysM2 were able to bind to skin lysate proteins (lanes 2, 4, and 5) and the binding of LysM1 was largely abolished when the sample was treated with PNGase F to remove the Nlinked oligosaccharides (lane 3).
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The Trichophyton rubrum genome contains six proteins containing two or more lysin M (LysM) domains. We have characterized two of these proteins, LysM1 and LysM2, and demonstrated that these proteins have the capacity to bind two substrates, chitin and N-linked oligosaccharides associated with human skin glycoproteins. We have characterized the indi...
Citations
... This number is higher than that reported in the reference strain CBS 118892. According to Kar et al. [64], two of the six proteins contained in the genome of T. rubrum (LysM1 and LysM2) were characterized and demonstrated that both could bind to chitin and N-linked oligosaccharide substrates associated with glycoproteins in human skin. Interestingly, Lopes et al. [65] reported that LysM-encoding genes such as TERG_05623, TERG_01015, TERG_03756, and TERG_05625 increased transcription levels when the pathogen was cultivated on a keratin medium. ...
Background: Trichophyton rubrum (T. rubrum) is the most common etiological agent of human dermatophytosis worldwide. T. rubrum has various phenotypic virulence factors that allow the infection to establish and evolve. Several enzymes, including keratinase, protease, lipase, deoxyribonuclease, elastase, and collagenase, are some of these virulence factors. This systematic review aimed to determine the main phenotypic virulence factors in T. rubrum. Methods: We performed a search in the databases PubMed, Scopus, and Scielo, including the words T. rubrum, virulence factors, lipase, phospholipase, keratinase, protease, deoxyribonuclease, elastase, collagenase, and biofilms. Results: We found 98 articles in the search databases. Twenty-eight were eliminated, as the information did not correspond to our purpose, and five articles were not retrieved. Thus, in the end, we included 65 papers. The articles highlighted many virulence factors associated with T. rubrum that could facilitate attachment, germination, formation of infection structures, penetration, and host colonization. Conclusions: Tolerance to high-stress environments and resistance to host defenses were reported. Some of the virulence factors found in the review were subtilisins, metalloprotease, oxidative stress fungal defenses (Catalases, Cu/Zn superoxide dismutase), hydrophobin, hydrolases, peptidase, chitinase, glucanase scw1, glutamate 5-kinase, GCN5-related N-acetyltransferase (GNAT family), heat shock proteins, LysM domains, other cell wall-associated, and biofilms. The review provided evident pathogenic mechanisms associated with T. rubrum ensuring its sustenance and survival.
... Kitin merupakan polimer golongan polisakarida yang berfungsi sebagai komponen penyokong atau pelindung, sehingga diduga adanya kitin dalam dinding sel jamur Trichophyton rubrum dapat meningkatkan resistensi terhadap zat antijamur. Pada penelitian Kar et al. (2019) jamur Trichophyton rubrum memiliki dua atau lebih domain lysin M, yaitu LysM 1 dan LysM 2. Kedua protein ini memiliki kemampuan untuk mengikat dua substrat yaitu kitin dan N-Linked oligosakarida dalam glikoprotein kulit manusia. Sehingga diduga protein LysM jamur Trichophyton rubrum dapat melindungi kitin dinding sel dari sistem kekebalan tubuh manusia. ...
Dermatophytosis is an infectious disease of the skin caused by one of the pathogenic agents of the fungus Trichophyton. Trichophyton rubrum is a dermatophyte fungus that is included in the anthropophilic classification, where transmission occurs through direct human-to-human contact. This experiment was conducted to determine the effectiveness of giving okra fruit extract (Abelmoschus esculentus) to the growth of Trichophyton rubrum using well method, media that is used to do that is SDA (Sabouraud Dextrose Agar) with various concentrations of 25 %, 50%, 75%, 100%. Based on the results of phytochemical tests, the active compounds contained in okra fruits extract are alkaloids, flavonoids, saponins, steroid, triterpenoids, phenolics and tannins. Variations in concentration of okra fruit extract and negative control tested against Trichophyton rubrum did not show the formation of inhibition zones in the media. Meanwhile for positive control using 2% ketoconazole, an inhibition zone 35 mm was formed. This research showed that Trichophyton rubrum was resistant to okra fruit extract.
... Secreted lipases and proteases are other important enzymes that not only serve as key virulence factors but also aid the dermatophytic fungi in surviving on the terminally differentiated keratinized layers of skin by deriving nutrients from it (Burmester et al. 2011;Achterman and (Table 4). Among other key virulence factors, LysM domain-containing proteins help in binding of the fungi to N-linked oligosaccharides on the human skin glycoproteins (Kar et al. 2019) and have been reported to be enriched in pathogenic fungi. Genome annotation and function prediction identified eight LysM domain-containing proteins each in TiCI12 and TiCI14, compared to seven in the RefSeq T. mentagrophytes MR816 strain. ...
In the current study, we report the genome sequence of two different clinical isolates from India, Trichophyton indotineae UCMS-IGIB-CI12 and Trichophyton indotineae UCMS-IGIB-CI14. The resulting genome assembly achieved a 143-fold coverage in 824 contigs for T. indotineae UCMS-IGIB-CI12 and a 136-fold coverage in 904 contigs for T. indotineae UCMS-IGIB-CI14. Both the clinical isolates contain a c.1342G>A mutation corresponding to Ala448Thr amino acid substitution in erg1 and exhibit an intermittent drug response to terbinafine. Comparative genomics analysis with available genomes of Trichophyton interdigitale/Trichophyton mentagrophytes species complex revealed a similar genome architecture and identified large number of genes associated with virulence and pathogenicity, namely, lipases, proteases, LysM domain-containing factors, carbon metabolism enzymes and cytochrome P450 enzymes, in all the genomes. An analysis of single amino acid polymorphisms (SAPs) in the protein sequences of subtilisin and lipase enzyme families identified a higher frequency of SAPs in functionally important proteins, Sub3 and Sub6 and their possible use in multilocus phylogenetic analysis of T. interdigitale/T. mentagrophytes species complex. The whole genome sequences of T. indotineae clinical isolates provided in this report will, hence, serve as a key reference point for investigation of clinical strains and emerging drug resistance among dermatophytes originating from different parts of the world.
... Furthermore, TERG_05627 and TERG_01873 were able to bind chitin and human N-linked oligosaccharides from skin glycoproteins. Thus, they may contribute to fungal adhesion and evasion from the innate host defense by shielding chitin structures [53]. Moreover, in Arthroderma benhamiae, hydrophobin HypA is a cell surface protein involved in fungal evasion from host recognition by neutrophils [41]. ...
The burden of fungal infections is not widely appreciated. Although these infections are responsible for over one million deaths annually, it is estimated that one billion people are affected by severe fungal diseases. Mycoses of nails and skin, primarily caused by fungi known as dermatophytes, are the most common fungal infections. Trichophyton rubrum appears to be the most common causative agent of dermatophytosis, followed by Trichophyton interdigitale. An estimated 25% of the world’s population suffers from dermatomycosis. Although these infections are not lethal, they compromise the quality of life of infected patients. The outcome of antidermatophytic treatments is impaired by various conditions, such as resistance and tolerance of certain dermatophyte strains. The adage “know your enemy” must be the focus of fungal research. There is an urgent need to increase awareness about the significance of these infections with precise epidemiological data and to improve knowledge regarding fungal biology and pathogenesis, with an emphasis on adaptive mechanisms to tackle adverse conditions from host counteractions. This review outlines the current knowledge about dermatophyte infections, with a focus on signaling pathways required for fungal infection establishment and a broad perspective on cellular and molecular factors involved in antifungal resistance and tolerance.
... It is supposed that LysM effectors in dermatophytes may take part in breaking down certain products of fungal cell walls which can serve as triggers of host immunity during invasion process, resulting in chitin mask, therefore avoiding host immunostimulation [11,36]. LysM domain can also facilitate adhesion of pathogens to human skin [37]. Figure 3 shows the LysM structure of E. floccosum and N. gypseum. ...
Epidermophyton floccosum is one of the most common agents of human superficial fungal infections, compared with genus Trichophyton and Microsporum, it possesses uniqueness in ecology traits and rarely causing hair infections. E. floccosum is so far the only representative species of genera Epidermophyton, and it is known as anthropophilic dermatophytes. To further reveal the genome sequences and clues of virulence factors, thus in this study, we sequenced the genome of E. floccosum (CGMCC (F) E1d), and performed comparative genomic analysis with other dermatophytes. It is revealed that E. floccosum owns the largest genome size and similar GC content compared with other dermatophytes. A total of 7565 genes are predicted. By comparing with the closest species N. gypseum, our study reveals that number and structure of adhesion factors, secreted proteases and LysM domain might contribute to the pathogenic and ecological traits of E. floccosum. Mating genes is also detected in genome data. Furthermore, we performed AFLP analysis trying to discuss intraspecific differences of E. floccosum, but no significant relationship is found between genotype and geographical distribution. Upon above, our study provides a deeper understanding and strong foundation for future researches about E. floccosum.
... Toll-like receptor (TLR) 2 was recently shown to play an important role in the phagocytosis of T. rubrum in monocytes, and reactive oxygen species and nitric oxide inhibited the growth of T. rubrum in cell lines in vitro [49,53]. T. rubrum lysin M proteins may help to shield the fungus and allow it to escape immune surveillance [54]. In addition to furthering our understanding of the pathogenesis, these findings have also provided a potential therapeutic target. ...
Zusammenfassung
Hereditäre Ichthyosen sind eine Gruppe von Genodermatosen, die entweder als nichtsyndromal oder syndromal klassifiziert werden. Nichtsyndromale Ichthyosen und das Keratitis‐Ichthyosis‐Taubheitssyndrom (keratitis, ichthyosis and deafness syndrome, KID‐Syndrom) prädisponieren für Pilzinfektionen. Diagnostik und Behandlung von Pilzinfektionen bei Ichthyosen sind herausfordernd. In dieser Übersicht fassen wir publizierte Ichthyose‐Fälle mit Pilzinfektion aus den letzten 50 Jahren zusammen. Bei Patienten mit Ichthyose in Kombination mit Pilzinfektion traten atypische Manifestationen wie Alopezie, Papeln und brüchige Nägel auf. Verschiedene Pathomechanismen wurden vorgeschlagen, darunter Mutationen Ichthyose‐relevanter Gene, die über verschiedene Signalwege zur Störung der Hautbarriere führen. Erkrankungen des Immunsystems, wie Atopie oder Störungen der angeborenen Immunität, tragen ebenfalls zur Anfälligkeit bei. Bestimmte Pilze können die Immunabwehr umgehen. Ausgedehnte und wiederkehrende Pilzinfektionen sind bei Ichthyose‐Patienten nicht selten, was die Heilung erschwert und systemische antimykotische Therapien erfordert. Etablierte und neue Ichthyosebehandlungen zielen darauf ab, die Barrierefunktion der Haut zur Vermeidung von Pilzinfektionen zu verbessern. Daher ist der enge Zusammenhang zwischen Ichthyose und Pilzinfektionen in der klinischen Praxis von entscheidender Bedeutung und erfordert ärztlicherseits mehr Aufmerksamkeit. Weitere Studien sind erforderlich, um beteiligte Mechanismen und sinnvolle Behandlungsstrategien zu erforschen.
... Toll-like receptor (TLR) 2 was recently shown to play an important role in the phagocytosis of T. rubrum in monocytes, and reactive oxygen species and nitric oxide inhibited the growth of T. rubrum in cell lines in vitro [49,53]. T. rubrum lysin M proteins may help to shield the fungus and allow it to escape immune surveillance [54]. In addition to furthering our understanding of the pathogenesis, these findings have also provided a potential therapeutic target. ...
Inherited ichthyoses are a group of genodermatoses classified as either nonsyndromic or syndromic. Nonsyndromic ichthyoses and keratitis, ichthyosis and deafness (KID) syndrome predispose to fungal infection. The diagnosis and treatment of fungal infections underlying ichthyoses are challenging. In this review, we summarize reported cases of ichthyosis with fungal infection over the past 50 years. Atypical manifestations such as alopecia, papules and brittle nails occurred in patients with ichthyosis combined with fungal infection. Various pathogenic mechanisms have been implicated, including mutations of ichthyosis‐related genes leading to disruption of the skin barrier via multiple pathways. Host immune disorders, including atopy and abnormal innate immunity also contribute to susceptibility. Specific fungi may escape the immune response. Extensive and recurrent fungal infections are not uncommon in patients with ichthyosis, making a cure more difficult and increasing the need for systemic antifungal therapy. Traditional and new ichthyosis treatments aiming to improve skin barrier function could help prevent fungal infection. In conclusion, the close relationship between ichthyosis and fungal infection is of vital importance in clinical practice and requires more attention from physicians. More studies are required to investigate the mechanisms and explore useful treatment strategies.
... In a similar way to RodA hydrophobin of Aspergillus fumigatus (29), the hypA protein of A. benhamiae forms a hydrophobic rodlet layer that enables conidia to avoid recognition by immune cells at an early stage of infection (21). Furthermore, other genes associated to the host-fungi interaction, mainly through genomic and/or transcriptomic analysis, were proposed: genes related to heat shock proteins (24), other enzymes that participate in keratin degradation (hydrolases, glucanases, chitinases, mannosyl transferases) (25), ergosterol metabolism and reproduction, and LysM domain proteins (19,23). Strikingly, various of these virulence factors might be transported to the extracellular space by extracellular vesicles (EVs), as it was demonstrated that T. interdigitale produces these structures in vitro (22). ...
Dermatophytoses (ringworms) are among the most frequent skin infections and are a highly prevalent cause of human disease worldwide. Despite the incidence of these superficial mycoses in healthy people and the compelling evidence on chronic and deep infections in immunocompromised individuals, the mechanisms controlling dermatophyte invasion in the skin are scarcely known. In the last years, the association between certain primary immunodeficiencies and the susceptibility to severe dermatophytosis as well as the evidence provided by novel experimental models mimicking human disease have significantly contributed to deciphering the basic immunological mechanisms against dermatophytes. In this review, we outline the current knowledge on fungal virulence factors involved in the pathogenesis of dermatophytoses and recent evidence from human infections and experimental models that shed light on the cells and molecules involved in the antifungal cutaneous immune response. The latest highlights emphasize the contribution of C-type lectin receptors signaling and the cellular immune response mediated by IL-17 and IFN-γ in the anti-dermatophytic defense and skin inflammation control.
... Several studies have shown that the radial colony growth of T. rubrum is regulated by the fungal cell wall integrity (23,24). The general mode of action that the known antifungal drugs inhibit T. rubrum is through downregulating the genes encoding for proteins involved in the cell wall integrity and function, thereby suppressing fungal growth (24)(25)(26)(27)(28)(29). The suppressive effect of AS-WSC on relative radial growth of T. rubrum found in our study is therefore also possibly caused by its down-regulative effect on cell-wall-related protein-encoding genes which is considered to be long-term stable effect. ...
In the present study, we examined antifungal activity of chitosan against Trichophyton rubrum (T. rubrum), which is a dermatophytic fungus and colonizes the upper layer of dead skin and causes athlete’s foot. Water-soluble chitosan oligosaccharide (AS-WSC), which had been prepared by the hydrolysis of high molecular weight water-soluble chitosan, was used in this study. The results upon screening, the AS-WSC inhibited T. rubrum, with zones of inhibition of 2% and 0.2% AS-WSC were 22 and 6 mm, respectively, while that of fluconazole was 30 mm. Minimal inhibitory concentration (MIC) values of AS-WSC was 1.25 mg/ml, while fluconazole showed MIC value of 2 μg/ml. Inhibition percentages of radial growth by 2% and 0.2% AS-WSC were 61% and 38%, respectively, while that of fluconazole was 73%. Two% and 0.2% AS-WSC treatment resulted in reduction of mycelium dry weights by 77% and 56%, respectively, while fluconazole reducing that by 84%. Our results suggest that AS-WSC can be a potential antifungal agent to treat infection by T. rubrum.
... Several studies have shown that the radial colony growth of T. rubrum is regulated by the fungal cell wall integrity (23,24). The general mode of action that the known antifungal drugs inhibit T. rubrum is through downregulating the genes encoding for proteins involved in the cell wall integrity and function, thereby suppressing fungal growth (24)(25)(26)(27)(28)(29). The suppressive effect of AS-WSC on relative radial growth of T. rubrum found in our study is therefore also possibly caused by its down-regulative effect on cell-wall-related protein-encoding genes which is considered to be long-term stable effect. ...
In the present study, we examined antifungal activity of chitosan against Trichophyton rubrum (T. rubrum), which is a dermatophytic fungus and colonizes the upper layer of dead skin and causes athlete’s foot. Water-soluble chitosan oligosaccharide (AS-WSC), which had been prepared by the hydrolysis of high molecular weight water-soluble chitosan, was used in this study. The results upon screening, the AS-WSC inhibited T. rubrum, with zones of inhibition of 2% and 0.2% AS-WSC were 22 and 6 mm, respectively, while that of fluconazole was 30 mm. Minimal inhibitory concentration (MIC) values of AS-WSC was 1.25 mg/ml, while fluconazole showed MIC value of 2 μg/ml. Inhibition percentages of radial growth by 2% and 0.2% AS-WSC were 61% and 38%, respectively, while that of fluconazole was 73%. Two% and 0.2% AS-WSC treatment resulted in reduction of mycelium dry weights by 77% and 56%, respectively, while fluconazole reducing that by 84%. Our results suggest that AS-WSC can be a potential antifungal agent to treat infection by T. rubrum.
