Chromoblastomycosis due to Cladosporium langeronii. Molecular diagnosis of an agent previously diagnosed as Fonsecaea pedrosoi.
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ABSTRACT:
SUBMITTER: Torres-Guerrero E
PROVIDER: S-EPMC6001112 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
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Chromoblastomycosis due to Cladosporium langeronii. Molecular diagnosis of an agent previously diagnosed as Fonsecaea pedrosoi.
Torres-Guerrero Edoardo E Arenas Roberto R Castro Rigoberto Hernández RH
Anais brasileiros de dermatologia 20180601 3
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Project description:We report herein a case of chromoblastomycosis caused by Fonsecaea (F.) pedrosoi in a 39-year-old male, who showed multiple, asymptomatic, scaly erythematous plaques on the left shin for 12 months. Histopathologically, chronic granulomatous inflammation and either sclerotic or muriform cells were observed. The fungal culture produced typical black colonies of F. pedrosoi. The DNA sequence of the internal transcribed spacer (ITS) region of the clinical sample was 100% match to that of F. pedrosoi IFM 47061 (GenBank accession number AB240943). The patient was treated with 200 mg of itraconazole daily, for 3 months. Skin lesions were improved. In Korea, only 9 cases of chromoblastomycosis, including this case, have been reported until now. The etiologic agent was F. pedrosoi in the majority of cases (6/9;67%). The incidence of chromoblastomycosis was slightly higher in female, and the upper limbs were more affected than the lower limbs in patients.
| S-EPMC3162270 | biostudies-literature
Project description:Fonsecaea pedrosoi is the main etiologic agent of chromoblastomycosis (CBM), one of the most prevalent subcutaneous mycosis in tropical and subtropical countries. CBM is a poorly characterized chronic infection that commonly starts after transcutaneous inoculation of conidia and saprophytic hyphae of F. pedrosoi. Recently, we have shown that unlike conidia, hyphae and muriform cells (the parasitic morphotype) of F. pedrosoi promotes an intense inflammatory response pattern in vivo, which comprises the production of an inflammasome-derived cytokine, IL-1β. Nonetheless, the mechanisms underlying IL-1β production and maturation upon F. pedrosoi infection and its functional output in the course of CBM remains unknown. We show here that F. pedrosoi hyphae, differently from conidia, induce IL-1β secretion in both bone marrow-derived dendritic cells and macrophages. Using inhibitors and knockout cells, we demonstrated that the mechanisms underlying IL-1β production by hyphae-infected macrophages were dependent on dectin-1, -2, and -3 receptors and the Syk-NF-kB signaling pathway. Furthermore, F. pedrosoi promoted a NLRP3-dependent inflammasome activation, which required potassium efflux, reactive oxygen species production, phagolysosomal acidification, and cathepsin B release as triggers. IL-1β processing and release was mediated primarily by caspase-1 and, to a lesser extent, by caspase-8-dependent cleavage. Finally, we showed using a murine CBM model that F. pedrosoi elicits a NLRP3-regulated IL-1β and interleukin-18 release in vivo, but without NLRP3 inflammasome activation interfering in the course of the experimental infection.
| S-EPMC5702042 | biostudies-literature
Project description:Transformation of Fonsecaea pedrosoi into muriform cells enhances the resistance against phagocytosis and elimination by host immune cells, and links to the chronicity of chromoblastomycosis. Here, we aim to determine whether the muriform cells can reproduce in tissue without reverse transformation into hyphal form by using an experimental nu/nu-BALB/c mouse model of chromoblastomycosis due to F. pedrosoi. During the whole 81-day observation period, most of the hyphal inocula had transformed into muriform cells at 75 days postinoculation and maintained as this parasitic morphology till 81 days postinoculation simultaneously with increased fungal loads in tissue and the worsening of footpad lesion. Scanning and transmitting electronic microscope examinations showed that the muriform cells obtained in tissue or induced in vitro can reproduce daughter cells by dividing, and, meanwhile, the daughter cells had the potential to produce buds and grow into hyphae reversely. Furthermore, exoenzyme examination suggested that the profile of exoenzymes constituted by muriform cells was quite different from that constituted by hyphae although the assay showed both of them had obvious metabolic activity. By contrast, most muriform cells in the footpad gradually transformed into the elongated hyphae without obvious infiltration of inflammatory cells during repeated intraperitoneal administration of cyclophosphamide (50 mg/kg, per every other day) from 50 to 80 days postinoculation. Therefore, we infer that F. pedrosoi can reproduce by dividing as muriform cells in mouse tissue, and the morphological transformation between hyphal form and muriform cells is possibly associated with the host immune status.
| S-EPMC7410477 | biostudies-literature
Project description:We report a fatal case of a chromoblastomycosis-like infection caused by a novel species of Fonsecaea in a 52-year-old immunocompetent Caucasian male from an area of chromoblastomycosis endemicity in Brazil. The patient had a 30-year history of slowly evolving, verrucous lesions on the right upper arm which gradually affected the entire arm, the left hemifacial area, and the nose. Subsequent dissemination to the brain was observed, which led to death of the patient. The internal transcribed spacer (ITS) and partial large subunit (LSU), BT2, and CDC42 genes of the isolates recovered from skin and brain were sequenced, confirming the novelty of the species. The species is clinically unique in causing brain abscesses secondary to chromoblastomycosis lesions despite the apparent intact immunity of the patient. Histopathologic appearances were very different, showing muriform cells in skin and hyphae in brain.
| S-EPMC4508443 | biostudies-literature
Project description:Patients with chromoblastomycosis (CBM) usually have a history of local skin damage related to outdoor activities, mainly manifested as chronic refractory proliferative pathologic changes. We report a case of a 56-year-old man with CBM, identified as Fonsecaea pedrosoi infection by fungal culture and gene sequencing. This patient was successfully treated with a regimen of oral itraconazole (ITZ) and terbinafine lasting 7 months. Through in vitro drug sensitivity tests, minimum inhibitory concentrations of amphotericin, ITZ, and terbinafine were 1 μg/ml, 0.25 μg/ml, and 1 μg/ml, respectively. In this case, terbinafine was found to be more effective than ITZ.
| S-EPMC7090106 | biostudies-literature
Project description:Among agents of chromoblastomycosis, Fonsecaea pugnacius presents a unique type of infection because of its secondary neurotropic dissemination from a chronic cutaneous case in an immunocompetent patient. Neurotropism occurs with remarkable frequency in the fungal family Herpotrichiellaceae, possibly associated with the ability of some species to metabolize aromatic hydrocarbons. In an attempt to understand this new disease pattern, were conducted genomic analysis of Fonsecaea pugnacius (CBS 139214) performed with de novo assembly, gene prediction, annotation and mitochondrial genome assembly, supplemented with animal infection models performed with Tenebrio molitor in Mus musculus lineages BALB/c and C57BL/6. The genome draft of 34.8 Mb was assembled with a total of 12,217 protein-coding genes. Several proteins, enzymes and metabolic pathways related to extremotolerance and virulence were recognized. The enzyme profiles of black fungi involved in chromoblastomycosis and brain infection were analyzed with the Carbohydrate-Active Enzymes (CAZY) and peptidases database (MEROPS). The capacity of the fungus to survive inside Tenebrio molitor animal model was confirmed by histopathological analysis and by presence of melanin and hyphae in host tissue. Although F. pugnacius was isolated from brain in a murine model following intraperitoneal infection, cytokine levels were not statistically significant, indicating a profile of an opportunistic agent. A dual ecological ability can be concluded from presence of metabolic pathways for nutrient scavenging and extremotolerance, combined with a capacity to infect human hosts.
| S-EPMC7417343 | biostudies-literature
Project description:A common theme across multiple fungal pathogens is their ability to impair the establishment of a protective immune response. Although early inflammation is beneficial in containing the infection, an uncontrolled inflammatory response is detrimental and may eventually oppose disease eradication. Chromoblastomycosis (CBM), a cutaneous and subcutaneous mycosis, caused by dematiaceous fungi, is capable of inducing a chronic inflammatory response. Muriform cells, the parasitic form of Fonsecaea pedrosoi, are highly prevalent in infected tissues, especially in long-standing lesions. In this study we show that hyphae and muriform cells are able to establish a murine CBM with skin lesions and histopathological aspects similar to that found in humans, with muriform cells being the most persistent fungal form, whereas mice infected with conidia do not reach the chronic phase of the disease. Moreover, in injured tissue the presence of hyphae and especially muriform cells, but not conidia, is correlated with intense production of pro-inflammatory cytokines in vivo. High-throughput RNA sequencing analysis (RNA-Seq) performed at early time points showed a strong up-regulation of genes related to fungal recognition, cell migration, inflammation, apoptosis and phagocytosis in macrophages exposed in vitro to muriform cells, but not conidia. We also demonstrate that only muriform cells required FcγR and Dectin-1 recognition to be internalized in vitro, and this is the main fungal form responsible for the intense inflammatory pattern observed in CBM, clarifying the chronic inflammatory reaction observed in most patients. Furthermore, our findings reveal two different fungal-host interaction strategies according to fungal morphotype, highlighting fungal dimorphism as an important key in understanding the bipolar nature of inflammatory response in fungal infections.
| S-EPMC5391973 | biostudies-literature
Project description:Chromoblastomycosis is a mutilating infection of the skin and subcutaneous tissues caused by melanized fungi belonging to the order Chaetothyriales. Proven cases of the main agent, Fonsecaea pedrosoi are mainly limited to (sub)tropical, humid climates of Latin and Central America and the Caribbean. Fonsecaea monophora has a global distribution along the equator. Cases outside the (sub)tropics have thus far mostly been considered to have been imported, but here we report the first endemic case by F. monophora from Argentina. Patient was a 82-year-old rural female worker from Corrientes, a province with a dry continental climate.
| S-EPMC5852295 | biostudies-literature