Mycopathologia最新文献

Although Scedosporium species may cause severe infections in immunocompromised patients, little is known about their pathogenic mechanisms. The thioredoxin reductases (TrxRs) of Scedosporium apiospermum are thought to play an important role in protecting the fungus against oxidative stress. The genes that encode these proteins are part of biosynthetic gene clusters (BGCs) which ensure the synthesis of non-ribosomal peptides. Due to the discrepancies between chemical studies and bioinformatic predictions regarding the product of the BGC comprising the TrxR-encoding gene SAPIO_CDS1830, a large-scale study of almost 300 fungal genomes was undertaken to search for BGCs that could potentially synthesize homodipeptides. Phylogenetic analysis of the amino acid sequence of the adenylation domain of a large number of non-ribosomal peptide synthases confirmed the assembly of two phenylalanine molecules. Synteny analysis clearly showed that this BGC ensures the synthesis of some aranotin-related hybrid compounds, called boydins. This BGC comprised 15 genes, including one encoding a polyketide synthase, which allows the synthesis of the polyketide chain attached to the dipeptide skeleton. The orthologues of all members of this BGC were also identified in all available Scedosporium genomes, as well as in other Sordariomycetes and even in some phylogenetically distant molds living as endophytes or plants pathogens, or on decaying wood. These secondary metabolites, which may therefore not be specific to the Scedosporium genus, could play a role in evasion of the fungus to the oxidative stress, as suggested by the overexpression of several members of this BGC in response to oxidative stress.

A 43-year-old man with myelodysplastic syndrome underwent umbilical cord blood transplantation (CBT). On day 4 post-transplantation, he developed right periorbital pain and oculomotor nerve palsy. Brain MRI revealed fluid accumulation in the sphenoid sinus and mucosal thickening in the right maxillary sinus. Given the extraordinarily early onset and neurological involvement, fungal meningitis, including mucormycosis, was suspected, and empirical high-dose liposomal amphotericin B (10 mg/kg/day) was initiated. Nasal discharge culture yielded Rhizomucor species, later identified as Rhizomucor miehei by polymerase chain reaction (PCR). Despite aggressive antifungal therapy, the patient's neurological condition deteriorated, and he died on day 49. Autopsy confirmed extensive rhino-cerebral mucormycosis with angioinvasion, and Mucorales DNA was detected in brain tissue by quantitative PCR. To our knowledge, this represents the first reported case of R. miehei infection occurring within days after transplantation, preceding neutrophil engraftment. This case highlights the importance of recognizing mucormycosis even in the immediate post-transplant period and underscores the limitations of antifungal therapy in the absence of surgical debridement.

Background: Despite important advancements in diagnostic modalities, routine use of therapeutic drug monitoring (TDM) and newer antifungal therapies, there is a paucity of contemporary data regarding clinical characteristics and outcomes of invasive aspergillosis (IA) in the United States.

Methods: Single-center, retrospective cohort study of hospitalized patients between 2015 and 2020, who had active hematological malignancy (HM) or had undergone transplantation and cellular therapy (TCT) and had probable or proven IA.

Results: Sixty-two patients with probable or proven IA, including 21 HM and 41 TCT, were identified. Forty-four percent of the cases corresponded to breakthrough IA. Bronchoalveolar lavage galactomannan was ≥ 1 in 71% and ≥ 0.5 in 88%, while serum galactomannan was ≥ 0.5 in only 34%. Among assessable patients (n = 59), 90-day partial or complete response to antifungal therapy occurred in 39%. All-cause mortality for the entire cohort was 22% at 30 days and 46% at 90 days. IA attributable mortality was 18% at 30 days and 38% at 90 days. Achieving therapeutic antifungal serum levels was associated with a reduction in all-cause mortality, while prior clinically significant CMV infection (aOR 9.65, 95% CI 1.34-69.6; P = 0.025) and relapsed/refractory hematological disease (aOR 8.5, 95% CI 2.23, 32.4; P = 0.002) were associated with higher IA attributable mortality.

Conclusions: Despite advancements in diagnosis and treatment, IA remains associated with poor outcomes in hematological patients in the contemporary era. Newer antifungals and improved strategies for monitoring and prevention of IA in these vulnerable patient populations are urgently needed.

Background: Trichosporon asahii is an opportunistic basidiomycetous yeast increasingly recognized as a cause of invasive infections in immunocompromised individuals, often associated with high morbidity and mortality. Its ability to adhere to host tissues and abiotic surfaces is considered a critical virulence factor, yet the molecular mechanisms underlying this adhesion remain poorly understood.

Objective: To characterize gene sequences in T. asahii belonging to the flocculin family with potential adhesive functions.

Methods: The homologous flocculin genes DHA1, DHA2, CPL1, and CFL1, previously described in Cryptococcus neoformans as being involved in cell adhesion, were identified within the T. asahii predicted proteome. Four T. asahii strains were analyzed: two reference strains (CBS2479 and CBS7631) and two clinical strains (L2585 and L773). Cells were grown in planktonic morphology and biofilms in RPMI + MOPS medium with 2% glucose. The predominant morphology of the cells was observed using bright-field optical microscopy, and total RNA was extracted. The relative expression of the four flocculin genes was analyzed by qRT-PCR and normalized using the 2-ΔΔCt method and the actin gene.

Results: The flocculin proteins showed high similarity and common domains with C. neoformans flocculins and other adhesins. The strains exhibited a variety of morphologies, with the T. asahii CBS2479 strain predominantly displaying yeast forms, while the T. asahii L2585 strain presented a higher quantity of hyphae. All flocculins bound to human proteins in the PriaA/Cpl1_fungi domain and/or to the Cpl1-like domain. T. asahii flocculins were downregulated when compared to the reference strain CBS2479, while the clinical strain L2585 exhibited the highest expression of the flocculin CFL1. During biofilm formation, DHA1 and CFL1 were highly expressed.

Conclusion: Flocculins were expressed according to specific yeast/hyphal morphology and were also more expressed in biofilms, indicating their association with biofilm maintenance and development.

Objectives: We aim to explore the factors that influence the varying prognostic outcomes of itraconazole treatment in patients with onychomycosis. A prediction model for treatment failure of onychomycosis to itraconazole was developed and validated.

Methods: This study is a prospective, case-cohort study of observational cases. Patient information meeting the inclusion criteria will be grouped and compared based on their outcomes six months after treatment.

Results: A total of 437 patients were enrolled in our study, and the following factors were correlated with prognosis: patient ages, duration of illness, number of affected nails, fungal species, clinical classification, nail thickness, nail involvement, and bathing frequency. Based on these variables, we constructed a predictive model for treatment failure in onychomycosis. The accuracy and precision of the prediction model for itraconazole treatment failure in onychomycosis were 0.936 and 0.924.

Conclusion: First, this study validated that multiple factors are associated with the prognosis of itraconazole pulse therapy for onychomycosis, suggesting that early treatment of the disease and attention to bathing habits can lead to better therapeutic outcomes. Second, based on the contribution of representative variables to the predictive power of the binary multivariate logistic regression model, it can help clinicians better understand the characteristics of patients with onychomycosis who experience treatment failure. These characteristics mainly include a longer disease duration, non-dermatophyte infections, multiple nail involvement, and significant psychological impact. Based on these features, it provides a reliable basis for determining the optimal treatment course of itraconazole pulse therapy for onychomycosis and whether additional treatment is needed.

Current guidelines recommend lumbar puncture (LP) in patients with pulmonary cryptococcosis (PC) to exclude central nervous system (CNS) involvement. However, recent multicenter data suggest that CNS dissemination is rare in immunocompetent, asymptomatic patients with low serum CrAg titers. And, although guidelines advocate induction therapy for severe PC, most patients in practice receive fluconazole monotherapy with favorable outcomes. This Perspective evaluates the gap between guideline-based universal intervention and real-world clinical practices, advocating for a risk-stratified management strategy. We outline clinical and laboratory features that may guide stratification and propose a pragmatic approach to streamline care and reduce unnecessary invasive procedures.

Introduction: Actinomucor elegans is an uncommon and underrecognized cause of invasive mucormycosis. While typically affecting immunocompromised individuals, cases have also emerged in trauma patients. This study presents a new case of cutaneous A. elegans infection and reviews the literature to characterize its clinical presentation, diagnostic challenges, and treatment outcomes.

Methods: We report a clinical case from our institution and conducted a narrative review of the literature. PubMed and Embase were searched through July 2025 for human cases of A. elegans. Studies were included if they provided clinical details on diagnosis or therapy. Data were extracted on demographics, comorbidities, infection site, diagnostics, treatments, and outcomes.

Results: Six unique cases were identified. Patients included both immunocompromised individuals and immunocompetent trauma victims. Reported infection sites included pulmonary, rhino-orbital, cutaneous, and disseminated forms. All cases were confirmed microbiologically, mainly through culture and sequencing. Liposomal amphotericin B was the primary antifungal agent, occasionally combined with other agents. Surgical debridement was performed in half the cases. The mortality rate was 50%; survival was associated with early diagnosis and antifungal therapy.

Conclusion: Actinomucor elegans is a rare but clinically significant mucormycete capable of causing severe infections in high-risk patients. Early recognition, combined microbiological diagnostics, and aggressive antifungal management are critical to improving patient outcomes.

To date, the transmission patterns and epidemiological characteristics of the zoonotic dermatophyte Microsporum canis in southwestern Guizhou, China, remain poorly understood. This study employed a multiphase approach integrating retrospective analysis of seven years of dermatophytosis data with a prospective cross-sectional survey of skin infections in cats and dogs conducted from February 2024 to August 2024. A total of 51 M. canis isolates-34 derived from humans and 17 from cats and dogs-were systematically analyzed to assess genotypic, phenotypic, physiological, and MAT gene distribution profiles. Sequencing of the ITS, tubb, and rpb2 loci revealed high genetic homogeneity across all isolates. With the exception of the human-derived strain JYP 21030b, in which amplification at the MAT locus failed, all isolates were identified as MAT1-1 genotype. Clinically, infections in both humans and animals were predominantly localized to the scalp. Physiological assessments revealed that animal-origin strains exhibited enhanced thermotolerance and more robust urease production compared to human-origin strains. Notably, evidence of distant hybridization between M. canis (JYP 21030b) and T. mentagrophytes var. interdigitale (JYP 21030a) was observed, accompanied by dynamic changes and diversity in mating type genes, which may correlate with distinct clinical and physiological traits. In conclusion, M. canis remains the predominant zoonotic dermatophyte responsible for dermatophytosis in humans and companion animals in this region. Despite limited molecular divergence, differences in enzymatic activity and thermal growth profiles suggest functionally driven phenotypic adaptability, with animal-origin strains demonstrating heightened environmental resilience and potential for host switching. Furthermore, the occurrence of interspecies hybridization offers a novel explanation for the paradox of low genetic variation coupled with observable phenotypic heterogeneity, thereby providing new insights into the transmission dynamics, ecological adaptation, and public health implications of M. canis.

Introduction: Talaromyces marneffei (TM) infection is an emerging global threat that increasingly affects immunocompromised individuals, including those with HIV/AIDS. This study aims to systematically analyze the clinical characteristics and treatment regimens of TM infection in HIV-positive patients, with a focus on exploring the optimal timing for antifungal therapy.

Design: A retrospective cross-sectional analysis was performed on 96 HIV-positive patients with TM infection from the Fourth People's Hospital of Nanning, Guangxi. The analysis included symptom manifestations, symptom combination patterns, laboratory test results, co-infection status, complications, and a comprehensive evaluation of treatment regimens, including medication types, combination strategies, and timing of administration.

Results: The study divided patients into three groups: rapid progression death group, stable progression death group, and survival group, to dissect the heterogeneity of the disease (the first two groups collectively constitute the Death Group, representing all deceased patients). Through statistical modeling and visual data exploration, a critical value of one month for medication timing was determined. Further multivariate analysis revealed that medication timing exceeding one month was identified as an independent risk factor for patient mortality. Renal impairment and serum albumin levels < 30 g/dL were identified as poor prognostic factors, while fever and hepatosplenomegaly were associated with a better prognosis, reflecting the body's immune response capacity.

Conclusions: The conclusions of this study provide empirical evidence for early empirical treatment of TM infection, explicitly defining the critical therapeutic time window as within 1 month of symptom onset. This information is crucial for improving patient outcomes and managing TM infection in immunocompromised populations.

Background: To characterize the clinical features and therapeutic outcomes of fungal keratitis caused by Plectosphaerella cucumerina.

Materials and methods: A retrospective analysis was conducted on 13 patients diagnosed with P. cucumerina keratitis from July 2018 to April 2024. Clinical manifestations, microbiological identification, antifungal susceptibility profiles, treatment regimens, and prognostic indicators were evaluated.

Results: All the 13 patients were farmers, and 6 of them had a history of trauma or the presence of a foreign body prior to the onset of symptoms. The main clinical manifestations were chronic progressive shallow corneal and middle stromal layer ulceration with dry ulcer surface, and moss formation was visible in 7 patients (7/13). No obvious immune ring structure and satellite lesions were observed in all patients. In vivo confocal microscopy (IVCM) showed that the mycelia showed medium strong reflection, some of them were changed like bamboo joints, most of them were 2-3 μm in diameter, and the arrangement was relatively neat and fasciculate. The Angle between the mycelia was small and most of them were acute angles. Drug sensitivity test showed that Amphotericin B, voriconazole and itraconazole were the main sensitive antifungal drugs. The main treatment was sensitive antifungal drugs combined with local lesion resection and voriconazole matrix injection. 2 cases with deep ulcers were treated with corneal transplantation.

Conclusions: P. cucumerina keratitis is relatively rare but distinct clinical entity. Diagnosis can be aided by corneal scraping, microbiological culture and IVCM. Emphasizing a comprehensive treatment approach involving medication, debridement, and surgical intervention is crucial to promote rapid healing of the ulcer.