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Fungal infections of the central nervous system (CNS) were considered rare until the 1970s. This is no longer true in recent years due to widespread use of corticosteroids, cytotoxic drugs and antibiotics. Immunocompromised patients with underlying malignancy, organ transplantations and acquired immune deficiency syndrome are all candidates for acquiring fungal infections either in meninges or brain. A considerable number of cases of CNS fungal infections even in immunocompetent hosts have been reported. A vast array of fungi may cause infection in the CNS, but barring a few, most of them are anecdotal case reports. Cryptococcus neoformans , Candida albicans, Coccidioides immitis. Histoplasma capsulatum are common causes of fungal meningitis; Aspergillus spp., Candida spp., Zygomycetes and some of the melanized fungi are known to cause mass lesions in brain. Few fungi like C. neoformans, Cladophialophora bantiana, Exophiala dermatitidis, Ramichloridium mackenzie, Ochroconis gallopava are considered as true neurotropic fungi. Most of the fungi causing CNS infection are saprobes with worldwide distribution; a few are geographically restricted like Coccidioides immitis . The infections reach the CNS either by the hematogenous route or by direct extension from colonized sinuses or ear canal or by direct inoculation during neurosurgical procedures.

To assess the prevalence of fungal keratitis, we conducted a retrospective study over 7 years (2005 through 2011) at a tertiary care center in North India. Effort has been made to analyze the disease burden, spectrum of agents and treatment history. The findings were compared with an earlier study at the same center for any change in the epidemiology of the disease. Microbiology records were screened at the Postgraduate Institute of Medical Education and Research, Chandigarh, India, to identify fungal keratitis cases, and available clinical records of those cases were analyzed. Of 2459 clinically suspected fungal keratitis cases, 765 (31 %) cases were direct microscopy confirmed. Of these microscopy-confirmed cases, fungi were isolated in 393 (51.4 %), with Aspergillus spp. ranked top ( n  = 187, 47.6 %), followed by melanized fungi ( n  = 86, 21.9 %) and Fusarium spp. ( n  = 64, 16 %). A male predominance of 78.7 % was noted with a peak in the incidence of fungal keratitis during post-monsoon season (September to November). A delay in diagnosis was significantly associated ( p  < 0.001) with keratitis cases due to melanized fungi. In comparison with an earlier study, higher isolation of melanized fungi was noted with a widening of the spectrum of agents identified. Thus, fungal keratitis due to Aspergillus spp. remains a serious ocular illness among the active male population in North India with relative rise of keratitis due to melanized fungi. The spectrum of agents causing fungal keratitis has broadened with many rare fungi that are implicated.

Background Inherited genetic deficiencies in the Caspase-associated recruitment domain-containing protein 9 (CARD9) lead to increased susceptibility of patients to opportunistic melanized fungi. Such infections are recalcitrant, and the fungus possibly acquires resistance under therapy. Objective To evaluate differences of in vitro antifungal susceptibility of strains of melanized fungi originating from patients with CARD9 deficiency versus strains from chronic patients with unclear genetic background. Methods We analyzed a total of 118 isolates, including 33 from patients with CARD9 deficiency, 80 from chronic patients with other undefined immunological features, and 5 environmental strains, all collected between 1997 and 2021. All isolates were identified by sequencing the ITS spacer of the rDNA operon. Broth microdilution susceptibility tests were performed according to CLSI guidelines (M38-A3document). Results MIC ranges of strains from infected patients having CARD9 deficiency and other individuals were mostly similar. However, comparing these two groups, the GM MICs of posaconazole, amphotericin B and fluconazole in the CARD9 group were statistically higher and the GM MICs of terbinafine lower than those of undefined genetic background group. The FICI of the CARD9 group were higher than those of the undefined group in the combination of caspofungin plus amphotericin B and amphotericin B plus fluconazole, but lower than the undefined group in the combination of itraconazole plus terbinafine. Conclusions The GM MICs for posaconazole, amphotericin B, and fluconazole were significantly elevated in the CARD9 group compared to the group with undefined chronic infections. For patients with refractory infections, conducting susceptibility testing before treatment can optimize the selection of the most effective therapeutic agent, and the combination therapy of caspofungin with amphotericin B or itraconazole may be considered the preferred treatment option.

Background: Due to more attentions paid to melanized fungi over the past few decades and under the background of the global coronavirus disease 2019 pandemic (COVID-19) the fact that the virus itself and the immunosuppressive agents such as glucocorticoids can further increase the risk of infections of deep mycoses, the number of patients with phaeohyphomycosis (PHM) has a substantial increase. Their spectrum is broad and the early diagnosis and treatments are extremely sticky. This study aims to more comprehensively understand the clinical features of phaeohyphomycosis in China over 35 years and to establish a more applicable systematical classification and severity grades of lesions to guide treatments and prognosis.Methods: We reviewed 174 cases of proven phaeohyphomycosis reported in Chinese and English language literature from 1987 to 2021 and we also made the accurate classification definitions and detailed information about the epidemiology, species of clinical dematiaceous fungi, minimum inhibitory concentration values, clinical features, treatments, and prognosis.Results: The mortality of cerebral, disseminated and pulmonary phaeohyphomycosis are 55%, 36%, and 25%. Nearly 19% of patients had poor quality of life caused by the complications such as disability, disfigurements, and blindness. The overall misdiagnosis rate of phaeohyphomycosis was 74%. Moderate to severe rashes are accounting for 82% of subcutaneous phaeohyphomycosis. The areas of the head and face are mostly affected accounting for 16% of severe rashes. Nearly 30% of invasive infections of phaeohyphomycosis are triggered by recurrent lesions. Voriconazole, itraconazole, amphotericin B deoxycholate (AmB-DOC), and terbinafine were most commonly used but diagnosis and treatments of phaeohyphomycosis remain challenging in reality.Conclusions: Our classifications are likely to be more practical and easier to popularize, and there are still also plenty of characteristics in these non-specific lesions. There’re no significant variations in cure rates, or death rates between three grades of lesions. But patients with severe rashes have longer courses and lower effective rates.

Melanized fungi are known for their remarkable resilience to environmental stress, largely attributed to the protective properties of melanin. In this study, we establish the black yeast Exophiala viscosa as a non-pathogenic, genetically tractable model for the scalable production and functional analysis of DHN-melanin (allomelanin). Cultivation in flasks and bioreactors yielded up to 8.6 g/L of melanin, with the majority tightly incorporated into the cell wall as “melanin ghosts”. Chemical analyses including FTIR, XPS, ssNMR, and EPR confirmed the identity of the pigment as allomelanin and revealed a structural association with chitin. Gene deletions of Pks1, Arp2, and Abr2 validated the DHN-melanin biosynthetic pathway and enabled the generation of pigment-deficient mutants. Functional assays demonstrated that melanin contributes significantly to UV and cold tolerance, while offering limited protection against γ-radiation, suggesting that other pigments,such as carotenoids, may also play a protective role. The unique redox properties, structural integrity, and scalability of melanin production in E. viscosa highlight its potential for bio-derived materials used in radiation shielding, environmental remediation, and thermal regulation. This work establishes E. viscosa as a promising chassis for melanin biomanufacturing and a valuable model for studying fungal melanins in the context of materials science and environmental resilience. Key points • Cultivation of E. viscosa in rich medium yielded up to 8.6 g/L of melanin. • Chemical and genetic analyses identified the pigment as allomelanin. • Melanin enhanced the tolerance of fungal cells to UV radiation and low temperatures.

Rhinocladiella similis is a melanized fungi involved in chromoblastomycosis. R. similis genome has never been sequenced, therefore we propose the first draft genome of R. similis.Rhinocladiella similis is a melanized fungi involved in chromoblastomycosis. R. similis genome has never been sequenced, therefore we propose the first draft genome of R. similis.

Background. Chromoblastomycosis (CBM) is a chronic fungal infection caused mainly by the melanized fungi Fonsecaea species. The chronic lesions may be predisposed to develop into cancer, the most serious complication of the disease. Methods. In this report, 7 cases of squamous cell carcinoma (SCC) resulting from chronic CBM in patients from Maranhấo in the Brazilian Amazon are described. Results. The 7 patients presented with SCC that resulted from chronic CBM, caused by Fonsecaea species >10 years' duration. The malignant lesions occurred independent of the antifungal therapy and all patients underwent curative amputation, except for 1 patient who developed metastases in the inguinal and intra-abdominal lymph nodes and thigh muscles. A majority of previous reports have focused on the malignant transformation of CBM described in only 1 patient each. This is a first report describing a group of patients from a single Brazilian state. Conclusions. Here, we provide new epidemiologic data on malignant CBM lesions, an endemic disease that is seemingly neglected worldwide. We reinforce the idea that typically chronic lesions may be predisposed to turn malignant.

Background Fungal brain abscesses in immunocompetent patients are exceedingly rare. Cladophialophora bantiana is the most common cause of cerebral phaeohyphomycosis, a dematiaceous mold. Radiological presentation can mimic other disease states, with diagnosis through surgical aspiration and growth of melanized fungi in culture. Exposure is often unknown, with delayed presentation and diagnosis. Case presentation We present a case of cerebral phaeohyphomycosis in a 24-year-old with no underlying conditions or risk factors for disease. He developed upper respiratory symptoms, fevers, and headaches over the course of 2 months. On admission, he underwent brain MRI which demonstrated three parietotemporal rim-enhancing lesions. Stereotactic aspiration revealed a dematiaceous mold on staining and the patient was treated with liposomal amphotericin B, 5-flucytosine, and posaconazole prior to culture confirmation. He ultimately required surgical excision of the brain abscesses and prolonged course of antifungal therapy, with clinical improvement. Conclusions Culture remains the gold standard for diagnosis of infection. Distinct microbiologic findings can aid in identification and guide antimicrobial therapy. While little guidance exists on treatment, patients have had favorable outcomes with surgery and combination antifungal therapy. In improving awareness, clinicians may accurately diagnose disease and initiate appropriate therapy in a more timely manner.

Purpose Cladophialophora bantiana is a wonted melanized fungus causing brain abscess. In past many cases were reported from Asia, particularly from India. Of late, there is a rise in cases in places besides Asia and hence a review of the cases is warranted. Methods We present a case of fatal cerebral phaeohyphomycosis caused by C. bantiana and conduct a systematic review of culture confirmed brain abscess due to C. bantiana reported between 2015 and 2022. Results Of the 39 cases found, majority (68%) were immunocompromised. The various clinical presentations were headache (53%), hemiparesis (34%), visual disturbance (25%), altered sensorium (18%), aphasia/dysarthria (12%) and seizures (9%). Isolated lesion was observed in 18 (60%) patients. In the sequence of occurrence, the lesions were in frontal (30%), temporal (27%) and parietal (20%) region. There were five cases with coinfections such as concurrent detection of Nocardia pneumonia in two cases, toxoplasma DNA in brain abscess, coexisting pulmonary Cryptococcus neoformans infection and coexisting Candida in a case of brain abscess in one case each. Surgical intervention was performed in 84% cases. Antifungal therapy included voriconazole (80%), liposomal amphotericin B (76%), 5-fluorocytosine (30%), posaconazole (10%), and amphotericin B deoxycholate (6%). The overall mortality was 50% with lower mortality (42%) in regions outside Asia compared to Asia (63.6%) though not statistically significant. Conclusions C. bantiana brain abscess is an emerging infection worldwide. Next generation sequencing is an upcoming promising diagnostic test. Early complete excision of the lesion with effective antifungals may improve the outcome.

The pathogenesis of chromoblastomycosis (CBM) is associated with Th2 and/or T regulatory immune responses, while resistance is associated with a Th1 response. However, even in the presence of IFN-γ, fungi persist in the lesions, and the reason for this persistence is unknown. To clarify the factors associated with pathogenesis, this study aimed to determine the polarization of the cellular immune response and the densities of cells that express markers of exhaustion in the skin of CBM patients. In the skin of patients with CBM, a moderate inflammatory infiltrate was observed, characterized primarily by the occurrence of histiocytes. Analysis of fungal density allowed us to divide patients into groups that exhibited low and high fungal densities; however, the intensity of the inflammatory response was not related to mycotic loads. Furthermore, patients with CBM exhibited a significant increase in the number of CD4+ and CD8+ cells associated with a high density of IL-10-, IL-17-, and IFN-γ-producing cells, indicating the presence of a chronic and mixed cellular immune response, which was also independent of fungal load. A significant increase in the number of PD-1+ and PD-L1+ cells was observed, which may be associated with the maintenance of the fungus in the skin and the progression of the disease.