FIG 2 - uploaded by Daniel Wagner CASTRO LIMA Santos
Content may be subject to copyright.
(a to c) Exophiala dermatitidis CBS 748.88. (a) Colony on malt extract agar (MEA) after 3 and 4 weeks of incubation at 30°C; (b) conidial head; (c) conidiophore and conidia. (d to f) Exophiala spinifera CBS 899.68. (d) Colony on MEA after 3 weeks of incubation; (e) conidiophore and conidia clustered at the apex of the conidiophore; (f) conidiophore and liberated conidia. (g to i) Cladophialophora carrionii CBS 166.54. (g) Colony on MEA after 3 weeks of incubation; (h) branching conidial system and conidial chains; (i) conidial chains. (j to l) Fonsecaea pedrosoi CBS 273.66. (j) Colony on MEA after 3 weeks of incubation; (k) conidiophores and conidia; (l) phialides and conidia. (m to o) Phialophora verrucosa BMU 07506. (m) Colony on MEA; (n) phialides and conidia; (o) flask-shaped phialides and conidia. (p to r) Rhinocladiella aquaspersa CBS 122635. (p) Colony on MEA after 3 weeks of incubation; (q) conidiophore and conidia; (r) young conidia and conidiophore. All cultures were incubated at 30°C.
Source publication
Chromoblastomycosis (CBM), also known as chromomycosis, is one of the most prevalent implantation fungal infections, being the most common of the gamut of mycoses caused by melanized or brown-pigmented fungi. CBM is mainly a tropical or subtropical disease that may affect individuals with certain risk factors around the world. The following charact...
Contexts in source publication
Context 1
... two Cladophialophora species causing CBM, i.e., C. carrionii and C. samoensis, form grayish-green, dry colonies that profusely sporulate, with conidia being arranged in long, densely branched chains composing a shrub-like conidial system (Fig. 2). Also, in these species, phialophora-like conidia may be produced on nutritionally poor media. Species are phenotypically identical; distinction is made by ITS sequencing (33). Phialophora verrucosa is monomorphic for flask-shaped phialides with large, dark, funnel-shaped collarettes at the top, from which slimy heads of ellipsoidal, one-celled conidia are produced. Colonies are olivaceous-black and grow moderately rapidly (24,25,34,68). Disseminated forms of the disease have also been reported but without unambiguous muriform cells in tissue (44), and thus, they may be considered PHM. Some similar cases in China concerned patients with CARD9 mutations ...
Context 2
... identification of individual species is done with the rDNA internal tran- scribed spacer (ITS) region (35). For distinction of closely related Fonsecaea or Phialo- phora species, an additional gene such as translation elongation factor 1 (TEF1) or a partial -tubulin gene (BT2) may be recommended (35, 57) (Fig. 2). The cytochrome P450 cluster involved in melanin synthesis and hydrocarbon degradation might play an important role in the virulence of the Chaetothyriales, which probably differs from the other virulence factors of fungi reported previously, such as Lac and HmgA (58), and other virulence factors (59-65). Likewise, the ACT1, BT2, and Cdc42 genes are effec- tively involved in cell cycle stages and the formation of the actin cytoskeleton (35), which has been related to morphogenetic switching to muriform cells, which are considered the invasive phase of agents of CBM (66) and which are also used for species distinction ...
Context 3
... genus Fonsecaea comprises four species that cause CBM: F. pedrosoi, F. mono- phora, F. nubica, and F. pugnacius. Fonsecaea monophora and F. pugnacius show significant neurotropism, eventually leading to dissemination to the brain and other organs (38,39,41) or causing primary brain infection without skin lesions, which are clinical forms of PHM, because no muriform cells are seen in tissues (40,67). All species of Fonsecaea have felt-like, gray-olivaceous colonies. Hyphae are regular, melanized, and branched in the apical part. Terminal cells show 1 to 4 denticles, each bearing a single-celled, broadly clavate conidium, which in turn produces 1 to 2 smaller conidia on denticles (34). Additionally, particularly in media poor in nutrients, phialides with slimy heads of conidia emerging from large collarettes may be produced (Fig. 2). The taxonomy of Fonsecaea was revised previously by de Hoog et al. (41) and Najafzadeh et al. (57). New species such as F. nubica and F. pugnacius were identified with sequences of the ITS and cdc42, BT2, and ACT1 genes, eventually supplemented with amplified fragment length polymorphism (AFLP) profiles (38,39). Pathogenic species of Fonsecaea present optimum development at 33°C, with a thermotolerance of growth at 37°C. These cardinal temperatures are slightly higher than those of strictly environ- mental species ...
Context 4
... leishmaniasis, rhinosporidiosis Viruses Verrucae, papillomas Helminths Filariosis Noninfectious Squamous cell carcinoma, mycosis fungoides, Bowen disease, psoriasis, sarcoidosis, systemic lupus erythematosus, mossy foot, and others however, culture identification is important because Fonsecaea species may be less sensitive to antifungals than C. carrionii (260,261). In addition, identification may contribute to data on the epidemiology and biodiversity of the etiological agents worldwide (262). When grown in routine culture media, most of the causative agents of CBM tend to form slow-growing, dark-pigmented colonies. Exceptions are sporadic cases caused by Exophiala spp., which may show an initial black-yeast aspect. CBM agents are not inhibited by cycloheximide or chloramphenicol, enabling the use of selective media to avoid rapidly growing contaminants. The incubation time is up to 6 weeks. Initial colonies are deep green, becoming velvety and darkening with time. In contrast to black yeasts, CBM agents lack an initial yeast phase. Microscopic examination allows identification to the genus level (Fig. 2). Further identification to the species level requires molecular sequencing, for which the rDNA ITS barcoding gene is recom- mended. In addition, taxonomic studies may apply specific genes, such as those encoding -tubulin, translation elongation factor 1 (35, 37, 54), and ...
Similar publications
Moulds and yeasts,so called dimorphic fungi, cause number of cutaneous infections.Transimission takes place via inoculation of agents as a result of injury or through hamatogenous spread, mostly from the lung. .Examples for inoculation mycoses are mycetoma caused by various fungi, chromoblastomycosis due to melanized or brown-pigmented fungi and sp...
Citations
... Correct identification to the species level and relevant reports on treatment outcomes are crucial for choosing appropriate antifungal therapy in a clinical setting. Several triazole derivatives, including itraconazole, posaconazole, voriconazole, and isavuconazole have been reported to be clinically effective against Cladophialophora species and other dematiaceous fungi [39,40]. Over the course of our patient's treatment, they were all used separately for different durations due to various side effects and limited drug availability. ...
Purpose
To report a case of endogenous endophthalmitis caused by the dematiaceous fungus Cladophialophora devriesii.
Methods
Observational case report and literature review.
Case presentation
A 73-year-old female with a history of chronic obstructive pulmonary disease presented with a red and painful left eye. Examination revealed anterior segment inflammation and vitritis, indicative of endophthalmitis. She underwent core vitrectomy and intravitreal injection of vancomycin and amphotericin B. The vitreous sample showed inflammatory cells and fungal hyphae, and systemic amphotericin B and itraconazole were commenced for fungal endophthalmitis. Targeted amplification of the sample for bacterial DNA (V2-V3 region of 16 S rDNA) was negative, but fungal DNA targets (ITS1 and ITS2) were present, and their sequences were consistent with Cladophialophora devriesii. Phenotypic characterisation and sequencing of ITS1 and ITS2, carried out on cultured fungus from the sample, also revealed Cladophialophora devriesii. She received repeated intravitreal injections of voriconazole, and based on the antifungal susceptibility results, her systemic medication was changed to posaconazole. After 12 months, the eye showed no signs of inflammation, and posaconazole therapy was discontinued. After 3 months without antifungal medication, the inflammation recurred, and she was restarted on antifungal therapy for an additional 20 months. Another recurrence occurred 3 months after discontinuation of treatment, and a repeat vitreous sample confirmed the presence of Cladophialophora devriesii. She was started on isavuconazole, but developed seclusio pupillae and painful secondary glaucoma. Due to the duration and severity of the infection, the eye was enucleated. Histopathology revealed persistent fungal elements at the ciliary processes and the posterior lens surface.
Conclusions
This second reported case of endogenous endophthalmitis caused by Cladophialophora devriesii illustrates the role of vitreous sampling and molecular methods in diagnosis and treatment of fungal endophthalmitis. Despite early diagnosis and prolonged local and systemic antifungal therapy, it was not possible to achieve long-term control of the fungal infection.
... MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions, or products referred to in the content. [7], with the main causative agents being species of the genus Fonsecaea sp., belonging to the bantiana clade [6,8]. ...
... Both CBM and PHM cause polymorphic and complex clinical manifestations, often associated with other diseases, making the differential diagnosis challenging [8,9,11]. Additionally, the high phenotypic similarity among species of the family Herpotrichiellaceae makes the identification of the causative agent through morphological analysis highly subjective, primarily dependent on the observerʹs experience [12]. ...
... Currently, the primary molecular identification technique for species within the family Herpotrichiellaceae is the genetic sequencing of the Internal Transcribed Spacer (ITS) of region of ribosomal DNA (rDNA) [8,15]. This method is typically confined to large research and surveillance centers, impeding access for individuals most affected by these infections to such services. ...
The Herpotrichiellaceae family is an important group of dematiaceous filamentous fungi, associated with a variety of pathogenic fungal species causing Chromoblastomycosis (CBM) and Phaeohyphomycosis (PHM), both with polymorphic clinical manifestations and worldwide incidence. Currently, the identification of this family and determination of the causative agent is challenging due to the subjectivity of morphological identification methods, necessitating the use of molecular techniques to complement diagnosis. In this context, genetic sequencing of the Internal Transcribed Spacer (ITS) has become the norm due to a lack of alternative molecular tools for identifying these agents. Therefore, this study aimed to develop PCR-Multiplex methodologies to address this gap. Sequences from the ITS and Large subunit (LSU) of ribosomal DNA were used, and after manual curation and in vitro analyses, primers were synthesized for the identification of the aforementioned targets. The primers were optimized and validated in vitro, resulting in two PCR-Multiplex methodologies: one for identifying the Herpotrichiellaceae family and the bantiana clade, and another for determining the species Fonsecaea pedrosoi and Fonsecaea monophora. Ultimately, the assays developed in this study aim to complement other identification approaches for these agents, reducing the need for sequencing, improving the management of these infections, and enhancing the accuracy of epidemiological information.
... There may be a hormonal or a genetic susceptibility, especially in patients with the HLA-A29 allele [1,6,7]. Numerous studies have been published, notably in Asia (Japan and China [8]), Madagascar [9] and Latin America (mostly Brazil and Mexico) [10]. ...
... We analyzed demographic data, clinical characteristics, histological and microbiological findings, treatments used and clinical evolution. We used the clinical severity grades proposed by Queiroz-Telles [10] to establish the clinical severity of the disease, as follows: ...
... There is no consensus about management of CBM. Surgical management by excision into healthy margins should always be proposed as first-line treatment whenever possible, as it usually leads to healing, particularly for mild forms [10]. Mohs micrographic surgery can also be proposed, with excellent efficacy and no distant recurrence [29], though access to this technique is limited due to its low availability, high cost, and the requirement for trained and available teams. ...
Chromoblastomycosis (CBM) is a chronic neglected fungal disease, usually met in tropical areas. French Guiana is a South American territory with limited epidemiological data. This retrospective study concerned all patients with CBM proven by at least one paraclinical examination and diagnosed in French Guiana between 1950 and 2023. In total, 23 patients were included, mostly males (87%) of Creole origin, living in the coastal region (87%) and involved in outdoor occupations (74%). Lesions were mostly observed on the lower limbs (78.3%), with a median time to diagnosis of four years. Laboratory tests included positive direct microscopic examinations (78.3%) and mycological cultures (69.6%), identifying 14 cases of Fonsecaea pedrosoi and one case of Exophiala janselmei. Various treatments were employed, including antifungals, surgery and combinations of both. In conclusion, CBM in French Guiana involves a different population than other subcutaneous mycoses such as Lobomycosis or Paracoccidioidomycosis, mostly found in the forest hinterland. Surgery should be recommended for recent and limited lesions. Itraconazole and terbinafine should systematically be proposed, either in monotherapy or in combination with surgery or cryotherapy.
... Chromoblastomycosis (CBM) and phaeohyphomycosis (PHM) are fungal infections primarily instigated by dematiaceous fungi, predominantly classified under the Herpotrichiellaceae family [1,2]. CBM is categorized by the World Health Organization as a neglected tropical disease, primarily due to its higher prevalence in economically disadvantaged or developing countries situated within tropical or subtropical regions [3][4][5]. ...
... CBM prevails endemically in countries spanning Latin America, Central America, Africa, and Asia, with a notable predilection for rural laborers [2,3,6,7]. In contrast, PHM is reported in diverse nations globally and exhibits a similar affinity for tropical and subtropical climates, predominantly affecting immunocompromised individuals, thus denoting it as an opportunistic infection [1,8,9]. ...
... Chromoblastomycosis and phaeohyphomycosis are both mycoses primarily transmitted through direct contact with contaminated materials, often resulting from traumatic injuries. These materials may encompass plant thorns, branches, soil, and various other organic components [1,2]. ...
Chromoblastomycosis (CBM) and phaeohyphomycosis (FEO) are infections caused by melanized filamentous fungal agents, primarily found in tropical and subtropical regions. Both infections pose significant challenges for the correct identification of the causative agent due to their morphological similarity, making conventional methods of morphological analysis highly subjective. Therefore, molecular techniques are necessary for the precise determination of these species. In this regard, this study aimed to contribute to a new methodology based on PCR-RFLP for the identification of agents causing CBM and FEO. Sequences from the Internal Transcribed Spacer (ITS) region were used to identify potential restriction enzyme sites in silico, followed by in vitro validation using the selected restriction enzymes. The obtained results were compared with species identification through morphological analyses and sequencing. The results demonstrated that the PCR-RFLP applied in this study accurately identified two major agents of chromoblastomycosis, Fonsecaea pedrosoi and Fonsecaea monophora, as well as Cladophialophora bantiana and Exophiala dermatitidis, both causative agents of phaeohyphomycosis. In this context, the proposed assay can complement current methods for identifying these species, aiding in diagnosis, and contributing to the proper management of these infections.
... Chromoblastomycosis (CBM) and phaeohyphomycosis (PHM) are fungal infections primarily instigated by dematiaceous fungi, predominantly classified under the Herpotrichiellaceae family [1,2]. CBM is categorized by the World Health Organization as a neglected tropical disease, primarily due to its higher prevalence in economically disadvantaged or developing countries situated within tropical or subtropical regions [3][4][5]. ...
... CBM prevails endemically in countries spanning Latin America, Central America, Africa, and Asia, with a notable predilection for rural laborers [2,3,6,7]. In contrast, PHM is reported in diverse nations globally and exhibits a similar affinity for tropical and subtropical climates, predominantly affecting immunocompromised individuals, thus denoting it as an opportunistic infection [1,8,9]. ...
... Chromoblastomycosis and phaeohyphomycosis are both mycoses primarily transmitted through direct contact with contaminated materials, often resulting from traumatic injuries. These materials may encompass plant thorns, branches, soil, and various other organic components [1,2]. ...
Chromoblastomycosis (CBM) and phaeohyphomycosis (FEO) are infections caused by melanized filamentous fungal agents, primarily found in tropical and subtropical regions. Both infections pose significant challenges for the correct identification of the causative agent due to their morphological similarity, making conventional methods of morphological analysis highly subjective. Therefore, molecular techniques are necessary for the precise determination of these species. In this regard, this study aimed to contribute to a new methodology based on PCR-RFLP for the identification of agents causing CBM and FEO. Sequences from the ITS region were used to identify potential restriction enzyme sites in silico, followed by in vitro validation using the selected restriction enzymes. The obtained results were compared with species identification through morphological analyses and sequencing. The results demonstrated that the PCR-RFLP applied in this study accurately identified two major agents of chromoblastomycosis, Fonsecaea pedrosoi and Fonsecaea monophora, as well as Cladophialophora bantiana and Exophiala dermatitidis, both causative agents of phaeohyphomycosis. In this context, the proposed assay can complement current methods for identifying these species, aiding in diagnosis, and contributing to the proper management of these infections.
... However, there are reports of its incidence in some countries in Europe, Canada, Russia, and Japan. It is caused by melanised fungi that are generally found in soil or plants and is classified as an orphan neglected disease [1][2][3]. The route of infection is frequently through a wound or lesion in the skin. ...
... The most common sites are the feet, knees, lower legs, and hands. However, it has also been reported in other sites or areas, such as the nose, auricular region, cornea, conjunctiva, scapular region, axillae, abdomen, buttocks, and as a phagedenic ulcer on the face [2,3]. ...
... Histopathologically, chromoblastomycosis is characterised by hyper-parakeratosis, pseudoepitheliomatous epidermal hyperplasia, microabscesses, pyogranulomatous reactions, and irregular acanthosis alternating with areas of atrophy. The dermis usually presents dense granulomatous inflammation with different grades of fibrosis, associated with mononuclear cells (histiocytes, lymphocytes, and plasma cells), epithelioid cells, giant cells, and polymorphonuclear cells [2,3]. ...
Chromoblastomycosis is a chronic granulomatous mycosis of the skin and subcutaneous tissue caused by traumatic inoculation with dematiaceous fungi. This disease primarily affects agricultural workers, who are mostly men. We present a case of chromoblastomycosis in a 63-year-old male farmer patient with dermatosis over 50 years of evolution, with warty, erythematous, and scaly plaques that predominate on the left hemithorax. Direct examination with potassium hydroxide (KOH) revealed numerous fumagoid cells. Amplification and sequencing of the internal transcribed spacer (ITS) and translation elongation factor 1-alpha (TEF-1a) gene revealed that chromoblastomycosis was caused by Cladosporium cladosporioides. The chromoblastomycosis was treated with itraconazole and fluconazole without any improvement, and amphotericin B was administered with partial improvement.
... Chromoblastomycosis is a neglected tropical disease typically found in endemic tropical and subtropical regions such as rural Latin America, the Caribbean, Africa, and Asia [1,2]. It is typically caused by transcutaneous inoculation of the fungus after handling an environmental source, such as soil, tree branches, plant debris, and wood. ...
... Chromoblastomycosis is a granulomatous fungal infection of the skin and subcutaneous tissue that is caused by dematiaceous fungi, primarily of the genera Fonsecaea, Phialophora, and Cladophialophora [1,2]. Endemic to tropical and subtropical regions, it is rarely found in the United States. ...
Chromoblastomycosis is a neglected tropical disease typically found in endemic tropical and subtropical regions. Herein, we discuss a rare case of a 55-year-old man in Texas who presented with an exophytic papule on the forearm, diagnosed to have chromoblastomycosis by shave biopsy and subsequent histopathological analysis. Treatment options for chromoblastomycosis include long-term oral antifungal therapy with itraconazole, physical modalities such as heat therapy in conjunction with oral antifungals, and surgical interventions such as cryosurgery or surgical excision.
... This form is multiseptated, pigmented and has a globe-shape morphology. Furthermore, the presence of muriform cells is the expression of the etiologic agent in the tissue [6]. However, the incubation period is unknown, and the evolution of CBM is slow and progressive. ...
... Furthermore, fungi can spread through tissues via the lymphatic system [7]. Depending on the immune response of the patient, the CBM develops into five different clinical forms: nodular, tumor type, verrucous, plaque, and cicatricial [6]. ...
Chromoblastomycosis (CBM) is a neglected human disease, caused by different species of pigmented dematiaceous fungi that cause granulomatous and suppurative dermatosis. This infection is difficult to treat and there are limited therapeutic options, including terbinafine, itraconazole, and tioconazole. Classic treatment is administered for a long period of time, but some patients do not respond properly, and therefore, such therapeutic approaches possess low cure rates. Therefore, it is vital to develop new strategies for the treatment of CBM. In this regard, it has been observed that the association of immunomodulatory molecules such as glucan with therapy carried out with antifungal drugs improves cutaneous lesions in comparison to treatment with antifungal drugs alone, suggesting that drug association may be an interesting and significant approach to incorporate into CBM therapy. Thus, the aim of this work was to associate classical antifungal therapy with the adjuvants imiquimod and acitretin. In the present case, we reported a patient with extensive CBM caused by Fonsaecae pedrosoi, that affected an extensive area of the right leg, that was left without treatment for 11 years. He was treated with a classical combination of itraconazole and terbinafine via the oral route plus topical imiquimod and oral acitretin, as an adjuvant therapy. After five months of treatment, a significant regression of verrucous plaques was observed, suggesting that the use of these adjuvants combined with the classical antifungal drugs, intraconazole plus terbinafine, can reduce treatment time and rapidly improve the patient’s quality of life. This result confirms that the use of coadjuvant drugs may be effective in the treatment of this infectious disease.
... The black yeasts and their relatives comprise numerous agents of human and (mostly cold-blooded) animal infection Queiroz-Telles et al. 2017). In the environment, the species seem to occur in specific microhabitats, and because of a low competitive ability towards other microorganisms, isolation of members of Chaetothyriales requires selective methods (Vicente et al. 2014). ...
Sugarcane (Saccharum officinarum, Poaceae) is cultivated on a large scale in (sub)tropical regions such as Brazil and has considerable economic value for sugar and biofuel production. The plant is a rich substrate for endo- and epiphytic fungi. Black yeasts in the family Herpotrichiellaceae (Chaetothyriales) are colonizers of human-dominated habitats, particularly those rich in toxins and hydrocarbon pollutants, and may cause severe infections in susceptible human hosts. The present study assessed the diversity of Herpotrichiellaceae associated with sugarcane, using in silico identification and selective isolation. Using metagenomics, we identified 5833 fungal sequences, while 639 black yeast-like isolates were recovered in vitro. In both strategies, the latter fungi were identified as members of the genera Cladophialophora, Exophiala, and Rhinocladiella (Herpotrichiellaceae), Cyphellophora (Cyphellophoraceae), and Knufia (Trichomeriaceae). In addition, we discovered new species of Cladophialophora and Exophiala from sugarcane and its rhizosphere. The first environmental isolation of Cladophialophora bantiana is particularly noteworthy, because this species up to now is exclusively known from the human host where it mostly causes fatal brain disease in otherwise healthy patients.
Supplementary Information
The online version contains supplementary material available at 10.1186/s43008-023-00124-7.
... This drug showed antifungal activity against phagocytosed C. neoformans, profoundly affected cryptococcal biofilms, and caused marked morphological changes, including reduced capsular dimensions [35]. As CBM agents do not form a capsule and histological sections do not demonstrate fungal biofilms in parasitism, but only in isolated muriform bodies [2,70], we suggest that the mebendazole activities against Cryptococcus and CBM agents are different. ...
Chromoblastomycosis (CBM) is a neglected human implantation mycosis caused by several dematiaceous fungal species. Currently available therapy is usually associated with physical methods, especially surgery, and with high refractoriness. Therefore, drug discovery for CBM is essential. Drug repositioning is a strategy used to facilitate the discovery of new treatments for several diseases. The aim of this study was to discover substances with antifungal activity against CBM agents from a collection of drugs previously approved for use in human diseases. A screening was performed with the NIH Clinical Collection against Fonsecaea pedrosoi. Ten substances, with clinical applicability in CBM, inhibited fungal growth by at least 60%. The minimum inhibitory concentration (MIC) of these substances was determined against other CBM agents, and the benzimidazoles albendazole, mebendazole and thiabendazole presented the lowest MIC values. The selectivity index, based on MIC and cytotoxicity of these substances, revealed albendazole to be more selective. To investigate a possible synergism of this benzimidazole with itraconazole and terbinafine, the chequerboard method was used. All interactions were classified as indifferent. Our current results suggest that benzimidazoles have repositioning potential against CBM agents. Albendazole seems to be the most promising, since it presented the highest selectivity against all dematiaceous fungi tested.
