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Frontiers in Cellular and Infection... 2023Chromoblastomycosis (CBM) is a form of chronic mycosis that affects the skin and mucous membranes and is caused by species of dematiaceous fungi including Exophiala...
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.
Topics: Humans; Antifungal Agents; Everolimus; Amphotericin B; Mycoses; Voriconazole; Microbial Sensitivity Tests; Fungi
PubMed: 36909734
DOI: 10.3389/fcimb.2023.1131416 -
American Journal of Ophthalmology Case... Mar 2023To report the initial case of microbial keratitis caused by , a rare cause of fungal keratitis.
PURPOSE
To report the initial case of microbial keratitis caused by , 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 and 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 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 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 .
PubMed: 36714019
DOI: 10.1016/j.ajoc.2023.101800 -
Medical Mycology Case Reports Mar 2023We 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...
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 phaeohyphomycosis. is an environmental mold recently described in human pathology in cases of chromoblastomycosis. This is the first case of subcutaneous phaeohyphomycosis due to in an immunocompromised patient.
PubMed: 36620427
DOI: 10.1016/j.mmcr.2022.12.003 -
Frontiers in Immunology 2022mutations are known to predispose patients to phaeohyphomycosis caused by different dematiaceous fungal species. In this study, we report for the first time a patient... (Comparative Study)
Comparative Study
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 , who harbored mutation. Through a series of and studies, especially a comparative transcriptome study, we compared this case with our former patient suffering from phaeohyphomycosis caused by . We showed that is prone to forming sclerotic bodies both and in knockout mice, and has a stronger immunogenicity than . These data preliminary demonstrated that besides host defense, fungal specificity also contributed to the clinical phenotype in deficient patients with dematiaceous fungal infections.
Topics: Animals; CARD Signaling Adaptor Proteins; Candidiasis, Chronic Mucocutaneous; Chromoblastomycosis; Disease Susceptibility; Humans; Mice; Mice, Knockout; Phaeohyphomycosis; Transcriptome
PubMed: 36159827
DOI: 10.3389/fimmu.2022.984093 -
Cureus Aug 2022Cutaneous chromoblastomycosis is a chronic subcutaneous fungal disease of the skin caused by , especially by , ,and species affecting the skin, lungs, intestines,...
Cutaneous chromoblastomycosis is a chronic subcutaneous fungal disease of the skin caused by , especially by , ,and species affecting the skin, lungs, intestines, stomach, and central nervous system. It is treated using itraconazole in mild cases and amphotericin B in severe cases. A six-year-old female child presented to the Dermatology Outpatient Department with pigmented brown to blackish tanned plaques and verrucous lesions on the face and extremities. These lesions were present for the past two and a half years and were slowly enlarging and involving other areas like the trunk. The lesions were proven on biopsy to be cutaneous blastomycosis. The patient was put on infusions of amphotericin B in a calculated pediatric dose. Her blood pressure and renal function tests were checked daily to avoid any electrolyte derangements, nephrotoxicity, and systemic infusion reactions caused by amphotericin B. Amphotericin B reduced the size of the cutaneous lesions, and treatment response was assessed on regular follow-ups. Chromoblastomycosis should be considered in the differential diagnosis to enable timely treatment and to prevent its lethal complications such as epidermoid carcinoma. Treatment should continue for two to three months until histopathology is negative to ensure complete eradication.
PubMed: 36158439
DOI: 10.7759/cureus.28286 -
Journal of Fungi (Basel, Switzerland) Sep 2022Patients with chromoblastomycosis (CBM) suffer chronic tissue lesions that are hard to treat. Considering that biofilm is the main growth lifestyle of several pathogens...
Patients with chromoblastomycosis (CBM) suffer chronic tissue lesions that are hard to treat. Considering that biofilm is the main growth lifestyle of several pathogens and it is involved with both virulence and resistance to antimicrobial drugs, we have investigated the ability of CBM fungi to produce this complex, organized and multicellular structure. and conidial cells were able to adhere on a polystyrene abiotic substrate, differentiate into hyphae and produce a robust viable biomass containing extracellular matrix. Confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM) showed the tridimensional architecture of the mature biofilms, revealing a dense network of interconnected hyphae, inner channels and amorphous extracellular polymeric material. Interestingly, the co-culture of each fungus with THP-1 macrophage cells, used as a biotic substrate, induced the formation of a mycelial trap covering and damaging the macrophages. In addition, the biofilm-forming cells of and were more resistant to the conventional antifungal drugs than the planktonic-growing conidial cells. The efflux pump activities of and biofilms were significantly higher than those measured in conidia. Taken together, the data pointed out the biofilm formation by CBM fungi and brought up a discussion of the relevance of studies about their antifungal resistance mechanisms.
PubMed: 36135688
DOI: 10.3390/jof8090963 -
JAAD Case Reports Oct 2022
PubMed: 36117779
DOI: 10.1016/j.jdcr.2022.07.047 -
Frontiers in Immunology 2022-related inherited immune disorders are a major risk factor for chronic disseminated fungal infection. In addition to pathogens of and dermatophytes, the environmental...
-related inherited immune disorders are a major risk factor for chronic disseminated fungal infection. In addition to pathogens of and dermatophytes, the environmental opportunists of the black yeast-like fungi are relatively frequent in this patient cohort. Particularly the genus is overrepresented. We investigated two isolates of a strain of residing in a 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; antifungal susceptibility had largely remained unaltered.
Topics: Antifungal Agents; CARD Signaling Adaptor Proteins; Humans; Immune System Diseases; Lysine; Melanins; Phialophora; Protein Processing, Post-Translational; Proteomics; Tandem Mass Spectrometry
PubMed: 36003392
DOI: 10.3389/fimmu.2022.966457 -
Frontiers in Microbiology 2022is a neotenic cave salamander, endemic to the Dinaric Karst and a symbol of world natural heritage. It is classified as "vulnerable" by the International Union for...
is a neotenic cave salamander, endemic to the Dinaric Karst and a symbol of world natural heritage. It is classified as "vulnerable" by the International Union for Conservation of Nature (IUCN) and is one of the EU priority species in need of strict protection. Due to inaccessibility of their natural underground habitat, scientific studies of the olm have been conducted mainly in captivity, where the amphibians are particularly susceptible to opportunistic microbial infections. In this report, we focused on the diversity of cultivable commensal fungi isolated from the skin of asymptomatic and symptomatic animals obtained from nature (20 specimens) and captivity (22 specimens), as well as from underground water of two karstic caves by direct water filtration and by exposure of keratin-based microbial baits and subsequent isolation from them. In total 244 fungal isolates were recovered from the animals and additional 153 isolates were obtained from water samples. Together, these isolates represented 87 genera and 166 species. Symptomatic animals were colonized by a variety of fungal species, most of them represented by a single isolate, including genera known for their involvement in chromomycosis, phaeohyphomycosis and zygomycosis in amphibians: , , , , , , , and . One symptomatic specimen sampled from nature was infected by the oomycete , the known causative agent of saprolegniosis. This is the first comprehensive report on cultivable skin mycobiome of this unique amphibian in nature and in captivity, with an emphasis on potentially pathogenic fungi and oomycetes.
PubMed: 35910647
DOI: 10.3389/fmicb.2022.926558 -
JFMS Open Reports 2022A 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...
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 species were identified. PCR and sequencing of (ITS1-5.8S-ITS2) confirmed 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 as an etiologic agent of phaeohyphomycosis in cats. In this case study, the species was identified using molecular tests.
PubMed: 35281676
DOI: 10.1177/20551169221077611