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Phialophora macrospora (CBS 273.37). a. Colonies grown on MEA for 3 wk; b. colonies grown on OA for 3 wk; c-k. micromorphology showing phialides and conidia.-Scale bar = 10 μm.
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Phialophora as defined by its type species P. verrucosa is a genus of Chaetothyriales, and a member of the group known as ‘black yeasts and relatives’. Phialophora verrucosa has been reported from mutilating human infections such as chromoblastomycosis, disseminated phaeohyphomycosis and mycetoma, while morphologically similar fungi are rather comm...
Citations
... Exophiala produced annellidic conidiogenesis and yeast-like states . Phialophora exhibited the basic morphological characteristics of conidial production through large phialidic conidiogenesis (Li et al., 2017). Rhinocladiella and Petriomyces share morphological characteristics of being polyblastic, as well as sympodial conidial formation on conidiogenous loci and aseptate conidia (Arzanlou et al., 2007). ...
... chinensis, and Phia. expanda can grow at temperatures of 37°C or higher Li et al., 2017). The growth temperature of herpotrichiellaceous fungi is often associated with clinical predilections with the species growing at 40°C often causing systemic infections (de Hoog et al., 2000;Badali et al., 2008). ...
Members of the family Herpotrichiellaceae are distributed worldwide and can be found in various habitats including on insects, plants, rocks, and in the soil. They are also known to be opportunistic human pathogens. In this study, 12 strains of rock-inhabiting fungi that belong to Herpotrichiellaceae were isolated from rock samples collected from forests located in Lamphun and Sukhothai provinces of northern Thailand during the period from 2021 to 2022. On the basis of the morphological characteristics, growth temperature, and multi-gene phylogenetic analyses of a combination of the internal transcribed spacer, the large subunit, and the small subunit of ribosomal RNA, beta tubulin and the translation elongation factor 1-a genes, the new genus, Petriomyces gen. nov., has been established to accommodate the single species, Pe. obovoidisporus sp. nov. In addition, three new species of Cladophialophora have also been introduced, namely, Cl. rupestricola, Cl. sribuabanensis, and Cl. thailandensis. Descriptions, illustrations, and a phylogenetic trees indicating the placement of these new taxa are provided. Here, we provide updates and discussions on the phylogenetic placement of other fungal genera within Herpotrichiellaceae.
... In our patient, Phialophora chinensis was cultured and identified by the laboratory. Although closely related to P. verrucosa, P. chinensis was recognized as a separate species in 2017 by Li et al. 9 These species can differ significantly in terms of pathogenicity and virulence. We report the initial case of P. chinensis fungal keratitis, describe our species identification method, and discuss management using a multimodal treatment approach. ...
... The ITS, partial LSU and partial TUBB gene were chosen to compare with sequences of the same loci in previous studies. 9,13 The DNA sequences) were used to perform BLASTn searches in GenBank (https://www.ncbi. nlm.nih.gov/) ...
... 19 Li et al. conducted a phylogenetic, morphologic, physiologic and ecological reassessment of the P. verrucosa complex resulting in the identification of four new species, which include P. chinensis, P. ellipsoidea, P. expanda and P. tarda. 9 Mycotic keratitis is encountered more frequently in immunocompromised hosts, such as transplant recipients, AIDS patients, and diabetics. 20 Local predisposing factors include trauma, especially with vegetable matter, contact lens wear, topical corticosteroid use, and ocular surface disorders. ...
Purpose:
To report the initial case of microbial keratitis caused by Phialophora chinensis, a rare cause of fungal keratitis.
Observations:
A 66-year-old gentleman with a complex right eye (OD) ocular history including herpes simplex virus infectious epithelial keratitis with subsequent neurotrophic keratopathy, and prior combined Candida albicans and parapsilosis fungal keratitis presented with pain OD in the absence of an antecedent trauma. The patient was found to have a filamentous fungal keratitis, which was subsequently cultured and identified as Phialophora chinensis by the laboratory. Despite topical and oral antifungal treatment based on sensitivities determined by the lab, the patient ultimately required intrastromal and subconjunctival antifungal injections, corneal crosslinking, and superficial keratectomy with amniotic membrane to clinically improve. The fungal keratitis recurred twice, with each occurrence rapidly progressing to corneal perforation. Months after the second penetrating keratoplasty, the patient's mental status declined due to multiorgan failure. An occult pulmonary malignancy was discovered during this hospital stay, and the patient was lost to follow-up after entering hospice.
Conclusions and importance:
We report a unique case of fungal keratitis caused by Phialophora chinensis and the subsequent management, including both medical and surgical interventions. Despite a multimodal treatment regimen, this case demonstrates the recalcitrant and potentially recurrent nature of fungal keratitis caused by P. chinensis.
... verrucosa, P. chinenis, P. macroaphora, P. americana), and Fonsecaea (F. pedrosoi, F. monophora) genera, among others (Najafzadeh et al., 2011;Li et al., 2017;Ahmed et al., 2021). While infections by these fungi generally begin in the skin, if they are not detected in the early stages of disease they can invade deep into the underlying tissues (Seas and Legua, 2022). ...
Introduction
Chromoblastomycosis (CBM) is a form of chronic mycosis that affects the skin and mucous membranes and is caused by species of dematiaceous fungi including Exophiala spp., Phialophora spp., and Fonsecaea spp. The persistence of this disease and limitations associated with single-drug treatment have complicated efforts to adequately manage this condition.
Methods
In this study, a microdilution assay was used to explore the synergistic antifungal activity of everolimus (EVL) in combination with itraconazole (ITC), voriconazole (VRC), posaconazole (POS), and amphotericin B (AMB) against a range of clinical dematiaceous fungal isolates.
Results
These analyses revealed that the EVL+POS and EVL+ITC exhibited superior in vitro synergistic efficacy, respectively inhibiting the growth of 64% (14/22) and 59% (13/22) of tested strains. In contrast, the growth of just 9% (2/22) of tested strains was inhibited by a combination of EVL+AMB, and no synergistic efficacy was observed for the combination of EVL+VRC.
Discussion
Overall, these findings indicate that EVL holds promise as a novel drug that can be synergistically combined with extant antifungal drugs to improve their efficacy, thereby aiding in the treatment of CBM.
... The Phialophora genus includes ascomycetous molds, subdivision Pezizomycotina, order Chaetothyriales and family Herpotrictrichiellaceae [11]. Phialophora verrucosa was first described as a pathogen in 1915 and is regularly described in infections such as chromoblastomycosis, phaeohyphomycosis and mycetoma [12]. This cosmopolitan species has been isolated in the environment [13,14]. ...
... Their analyses corrected the species identification of several strains of Philophora verrucosa to Phialophora chinensis. Philophora chinensis was found mainly in the environment in China (wood, bark, soil, wheat, bamboo) [12]. P. chinensis was first reported as a pathogen in the form of chomoblastomycosis in a 53-year-old immunocompetent farmer in Mexico. ...
We report a case of subcutaneous mycosis in the form of a subcutaneous cyst of the index finger, successfully treated by surgery and posaconazole in an 84-year-old female kidney transplant patient. Intra-operative mycological analysis enabled the diagnosis of Phialophora chinensis phaeohyphomycosis. Phialophora chinensis is an environmental mold recently described in human pathology in cases of chromoblastomycosis. This is the first case of subcutaneous phaeohyphomycosis due to Phialophora chinensis in an immunocompromised patient.
... In this study we report, for the first time, a patient harboring the CARD9 mutation with chromoblastomycosis caused by Phialophora expanda, which is a fungus from the Phialophora verrucosa complex according to our previous phylogenetic studies (5). We designed a series of in vivo and in vitro studies to compare this case with our former patient suffering from phaeohyphomycosis caused by P. americana, from the same complex (5). ...
... In this study we report, for the first time, a patient harboring the CARD9 mutation with chromoblastomycosis caused by Phialophora expanda, which is a fungus from the Phialophora verrucosa complex according to our previous phylogenetic studies (5). We designed a series of in vivo and in vitro studies to compare this case with our former patient suffering from phaeohyphomycosis caused by P. americana, from the same complex (5). We preliminarily demonstrated that besides host defense, fungal specificity also contributed to the clinical phenotype in patients with dematiaceous fungal infections. ...
... PCR products were sequenced by Sangon Biotech Co. Ltd. (Shanghai, China). The alignments and phylogenetic reconstructions were performed in accordance with Li et al. (5). ...
CARD9 mutations are known to predispose patients to phaeohyphomycosis caused by different dematiaceous fungal species. In this study, we report for the first time a patient of chromoblastomycosis caused by Phialophora expanda, who harbored CARD9 mutation. Through a series of in vivo and in vitro studies, especially a comparative transcriptome study, we compared this case with our former patient suffering from phaeohyphomycosis caused by Phialophora americana. We showed that P. expanda is prone to forming sclerotic bodies both in vitro and in Card9 knockout mice, and has a stronger immunogenicity than P. americana. These data preliminary demonstrated that besides host defense, fungal specificity also contributed to the clinical phenotype in CARD9 deficient patients with dematiaceous fungal infections.
... This was however not confirmed by in vitro analysis, showing an increase of melanization in BMU 04928. The downregulation is rather counter-intuitive, as melanin is generally judged to be a virulence factor protecting the cell against hyperoxygenic action of the macrophage (36,37), and in vitro melanization had increased (Supplementary Figure 5). Song et al. (38) showed that subjecting cells of Exophiala dermatitidis may lead to loss of melanin, which corresponds with frequent occurrence of hyaline cells of melanized fungi in tissue (39). ...
... Phialophora verrucosa is probably an environmental opportunist (37). With prolonged presence in the stressful, non-optimal habitat provided by the human host, a certain degree of adaptive micro-evolution might be expected from progenitor (BMU 00512) to derived isolate (BMU 04928). ...
CARD9-related inherited immune disorders are a major risk factor for chronic disseminated fungal infection. In addition to pathogens of Candida and dermatophytes, the environmental opportunists of the black yeast-like fungi are relatively frequent in this patient cohort. Particularly the genus Phialophora is overrepresented. We investigated two isolates of a strain of P. verrucosa residing in a CARD9 patient, sampled with a period of ten years apart. Genomes, melanization and antifungal susceptibility of progenitor and derived strains were compared, and potential adaptation to the host habitat was investigated with proteomic techniques using post-translational modification as a proxy. Global lactylation analysis was performed using high accuracy nano-LC-MS/MS in combination with enrichment of lactylated peptides from digested cell lysates, and subsequent peptide identification. The genome of the derived isolate had accumulated 6945 SNPs, of which 31 were detected in CDS. A large number of identified proteins were significantly enriched, e.g. in melanin biosynthesis. A total of 636 lactylation sites on 420 lactylated proteins were identified, which contained in 26 types of modification motifs. Lysine lactylation (Kla) was found in 23 constituent proteins of the ribosome, indicating an impact of Kla in protein synthesis. Twelve lactylated proteins participated in pathogenicity. A protein-protein interaction (PPI) network analysis suggested that protein lactylations are widely distributed influencing various biological processes. Our findings reveal widespread roles for lysine lactylation in regulating metabolism and melanin biosynthesis in black fungi. Several large rearrangements and inversions were observed in the genome, but genomic changes could not be linked to adaptation or to known clinically relevant properties of progenitor to derived isolate; in vitro antifungal susceptibility had largely remained unaltered.
... Together, these species make up the 'Phialophora verrucosa species complex'. 12,13 They are morphologically similar but with some variations in growth rate and subtle differences in the shape of the phialides and their collarettes. 12 However, P americana tends to have deeper collarettes than the other species in the complex. ...
... 12,13 They are morphologically similar but with some variations in growth rate and subtle differences in the shape of the phialides and their collarettes. 12 However, P americana tends to have deeper collarettes than the other species in the complex. 14 In a study of the biodiversity of clinical and environmental strains using molecular tools, 12 of 118 strains previously identified morphologically as P verrucosa, only six belonged to that species and about 50 strains were identified as P americana. ...
... 14 In a study of the biodiversity of clinical and environmental strains using molecular tools, 12 of 118 strains previously identified morphologically as P verrucosa, only six belonged to that species and about 50 strains were identified as P americana. 12 Morphological differences between the Phialophora species are not easy to distinguish; therefore, in medical healthcare centers where identification is by phenotypic methods, the isolates that come from clinical cases are usually attributed to P verrucosa. 15 Unlike Cladophialophora carrionii and Fonsecaea species, which exclusively produce chromomoblastomycosis, P verrucosa (and other species of Phialophora) produces a wide range of clinical conditions in humans, such as subcutaneous and disseminated phaeohyphomycosis, eumycetoma, keratitis and endophthalmitis. ...
Case summary:
A 10-year-old male neutered domestic shorthair cat from Quilmes (Province of Buenos Aires, Argentina) presented at the Infectious Diseases and Parasitology Unit with a hyperpigmented nodule of 5 cm diameter on the nasal plane with a small ulceration of more than 1 year's evolution. A scaly and hyperpigmented alopecic lesion of 3 cm in diameter was found on the lower edge of the tail. The patient was under immunosuppressive therapy with corticosteroids for lymphoplasmacytic duodenitis. Samples of the lesion present on the nasal plane were taken under a surgical procedure. In the wet mount preparations, pigmented irregular hyphae were observed. They developed dark colonies when cultured on Sabouraud medium. On micromorphology, structures compatible with Phialophora species were identified. PCR and sequencing of ITS (ITS1-5.8S-ITS2) confirmed Phialophora americana as the etiologic agent. A therapeutic scheme that included a combination of itraconazole oral solution (1.5 mg/kg PO q12h) with terbinafine (30 mg/kg PO q24h) was indicated for a period of 10 months. The patient died of complications resulting from its underlying disease.
Relevance and novel information:
As far as the authors are aware, this is the first study to report P americana as an etiologic agent of phaeohyphomycosis in cats. In this case study, the species was identified using molecular tests.
... Together, these species make up the 'Phialophora verrucosa species complex'. 12,13 They are morphologically similar but with some variations in growth rate and subtle differences in the shape of the phialides and their collarettes. 12 However, P americana tends to have deeper collarettes than the other species in the complex. ...
... 12,13 They are morphologically similar but with some variations in growth rate and subtle differences in the shape of the phialides and their collarettes. 12 However, P americana tends to have deeper collarettes than the other species in the complex. 14 In a study of the biodiversity of clinical and environmental strains using molecular tools, 12 of 118 strains previously identified morphologically as P verrucosa, only six belonged to that species and about 50 strains were identified as P americana. ...
... 14 In a study of the biodiversity of clinical and environmental strains using molecular tools, 12 of 118 strains previously identified morphologically as P verrucosa, only six belonged to that species and about 50 strains were identified as P americana. 12 Morphological differences between the Phialophora species are not easy to distinguish; therefore, in medical healthcare centers where identification is by phenotypic methods, the isolates that come from clinical cases are usually attributed to P verrucosa. 15 Unlike Cladophialophora carrionii and Fonsecaea species, which exclusively produce chromomoblastomycosis, P verrucosa (and other species of Phialophora) produces a wide range of clinical conditions in humans, such as subcutaneous and disseminated phaeohyphomycosis, eumycetoma, keratitis and endophthalmitis. ...
A 10-year-old male neutered domestic shorthair cat from Quilmes (Province of Buenos Aires, Argentina) presented at the Infectious Diseases and Parasitology Unit with a hyperpigmented nodule of 5 cm diameter on the nasal plane with a small ulceration of more than 1 year’s evolution. A scaly and hyperpigmented alopecic lesion of 3 cm in diameter was found on the lower edge of the tail. The patient was under imunosuppressive therapy with corticosteroids for lymphoplasmacytic duodenitis. Samples of the lesion present on the nasal plane were taken under a surgical procedure. In the wet mount preparations, pigmented irregular hyphae were observed.
They developed dark colonies when cultured on Sabouraud medium. On micromorphology, structures compatible with Phialophora species were identified. PCR and sequencing of ITS (ITS1-5.8S-ITS2) confirmed Phialophora americana as the etiologic agent. A therapeutic scheme that included a combination of itraconazole oral solution
(1.5 mg/kg PO q12h) with terbinafine (30 mg/kg PO q24h) was indicated for a period of 10 months. The patient died of complications resulting from its underlying disease.
... The growth and color of Valentiella colonies resemble those of some Exophiala species (Song et al. 2017). It is similar to fungi, producing yeast-like and torulose cells, such as Phialophora species, which have been reported to have a yeast phase in culture and produce torulose hyphae and muriform-like cells (Li et al. 2017). Despite these genera sharing colony similarities with some of their species, they are not phylogenetically related to Valentiella. ...
Bromeliads have shown to be an excellent reservoir for fungi, especially yeasts and yeast-like fungi. Three strains were obtained from healthy leaves of Canistrum improcerum and Aechmea muricata (Bromeliaceae) in the Atlantic Forest of the Brazilian northeastern region. They were characterized morphologically, biochemically/physiologically, and based on the sequence-based phylogenetic species concept with analysis of the nrLSU and the ITS regions and the translation elongation factor EF-1 alpha (TEF1) gene. Based on our findings, a new genus, and species, namely, Valentiella maceioensis (Herpotrichiellaceae, Chaetothyriales, Ascomycota), was introduced for these isolates. The new taxa are mainly characterized by their black yeast-like morphology, with a mycelium consisting of torulose hyphae, conidiophores that were straight or slightly flexuous, septate, and chains of brown to dark brown fusoid-ellipsoid cells; conidiogenous cells fusoid-ellipsoid, 0–1-septate, brown to dark brown, having apical scars at the apex, and producing heads of conidia; conidia ellipsoid, subglobose to globose, light brown to brown with age, occasionally having basal scars. In the yeast-like phase, pseudohyphae and true hyphae are rarely formed while budding cells are present, and fermentation is not observed.
... No obvious genomic difference has yet been found to explain pathogenic versus non-pathogenic nature of species in the carrionii-clade, which might indicate that implantation infections by these fungi are coincidental and denote opportunistic nature rather than true pathogenicity [11][12][13]. The same holds true for P. verrucosa and relatives: strains have been derived from environmental habitats and from clinical samples, and therefore, it is difficult to distinguish clinically relevant entities from non-virulent members [14,15]. ...
... In contrast to its related species, C. carrionii, P. verrucosa has been reported to be involved in a wide range of clinical conditions, among which are disseminated and subcutaneous phaeohyphomycosis, eumycetoma, keratitis, and endophthalmitis [10,14,16,17]. Infections attributed to P. verrucosa have mostly been reported from apparently healthy individuals from subtropical climate zones including China, Japan, Colombia, Brazil, Mexico, U.S.A., and Libya [8,14,[18][19][20]. ...
... In contrast to its related species, C. carrionii, P. verrucosa has been reported to be involved in a wide range of clinical conditions, among which are disseminated and subcutaneous phaeohyphomycosis, eumycetoma, keratitis, and endophthalmitis [10,14,16,17]. Infections attributed to P. verrucosa have mostly been reported from apparently healthy individuals from subtropical climate zones including China, Japan, Colombia, Brazil, Mexico, U.S.A., and Libya [8,14,[18][19][20]. Occasionally, patients have immunological disorders such as CARD9 mutation [21,22], impairing differentiation of Th 17 immune cells and leading to extended, erosive case of phaeohyphomycosis [22]. ...
Chromoblastomycosis is a chronic severely mutilating disease caused by fungi of the order Chaetothyriales. Classically, Phialophora verrucosa has been listed among these etiologic agents. This species is known to occur in the environment and has been found to cause other infections like phaeohyphomycosis, while reported cases of chromoblastomycosis are scant. Phialophora is phylogenetically diverse, and thus retrospective confirmation of etiology is necessary. We studied ten proven cases of chromoblastomycosis from Mexico and further analyzed the population genetics and genomics of the Phialophora species to understand their pathogenicity and predilection. The clinical strains were molecularly identified as Phialophora americana (n = 4), Phialophorachinensis (n = 4), and Phialophora macrospora (n = 2). No genetic distinction between clinical and environmental strains was possible. Further analysis of strains from diverse origins are needed to address eventual differences in virulence and niche predilection between the species.
