Mycopathologia最新文献

Background: Otomycosis is a common fungal infection of the external auditory canal (EAC), with a higher incidence in tropical and subtropical regions. Epidemiological information on otomycosis in southern China is limited. This study aimed to characterize the clinical manifestations, otoendoscopic features, and pathogen distribution of otomycosis in southern China.

Methods: A retrospective analysis was conducted of 192 confirmed cases of otomycosis among patients at a tertiary hospital in Guangzhou, southern China.

Results: The most common presentation was ear pruritus, followed by hearing loss, aural fullness, otorrhea, tinnitus, and otalgia. Unilateral infection was more common than bilateral infection. The EAC was the primary site affected. Characteristic findings included crusts, congestion, fungoid substance, exudate, and swelling. These features (especially crusts, congestion, swelling, and fungoid substance) were significantly associated with fungal positivity. Of the 110 cases in which fungal pathogens were identified, the majority (103, 93.64%) were Aspergillus species including A. terreus (n = 69), A. flavus (n = 16), A. niger (n = 13), A. sclerotiorum (n = 2), A. oryzae (n = 1), A. sydowii (n = 1) and A. tamarii (n = 1); Candida species accounted for 4 isolates (3.64%), and one isolate each was identified for Cladophialophora, Trichophyton, and Scopulariopsis species (0.91%).

Conclusion: These findings provide region-specific insights that are crucial for guiding effective clinical diagnosis, prevention and empirical antifungal therapy. Antifungal therapy covering Aspergillus should be prioritized in this high-incidence area.

The yeasts of the genus Malassezia are part of the normal skin microbiota of a wide range of warm-blooded animals including humans. Within this genus, Malassezia pachydermatis is commonly found in the normal skin microbiota of a variety of animal hosts. Malassezia yeasts are considered lipid-dependent due to their inability to synthesize long chain fatty acids de novo. While M. pachydermatis is typically able to grow on Sabouraud's agar (SGA) without lipid supplementation, certain strains display an atypical lipid dependency and are unable to grow on SGA. The aim of this work was to study the genomic differences between atypical M. pachydermatis strains unable to grow on SGA and the reference strain. The genomes of three atypical lipid-dependent M. pachydermatis strains were sequenced using Illumina technology and compared with the reference genome of M. pachydermatis neotype strain CBS 1879. A total of 397 small variants with a high or moderate impact on the protein were observed in genes involved in lipid metabolism. Of those small variants observed we highlight the ones observed in 12 out of the 13 genes encoding secretory lipases and in the CKI1 gene that is unique to M. pachydermatis within the genus. The analysis of those small variations suggested a variation in their ability to adapt to environmental changes and their requirements to grow in different culture media.

The first case of Talaromyces marneffei infection diagnosed by next-generation sequencing (NGS) was reported in 2018. By 31st December 2024, the number of T. marneffei infections picked up by NGS has increased to a total of at least 241. Most cases were reported from China, reflecting both the regional importance of this infection and its widespread use of NGS for laboratory diagnosis of infectious diseases. Among the cases with clinical details reported, 136 were HIV-negative, which was probably the main reason why T. marneffei was not suspected and the diagnosis was subsequently made with the use of NGS. For these 136 HIV-negative patients, 62 were confirmed to have other forms of immunodeficiencies, such as anti-interferon gamma autoantibodies and post-renal/liver transplantation. The clinical presentations were usually non-specific. At least 18 patients were clinically diagnosed as tuberculosis, and empirical anti-tuberculosis therapy was prescribed to 13 patients and NGS was performed because they did not respond to or deteriorated while on anti-tuberculosis treatment. Apart from infectious diseases, at least another 11 patients were initially misdiagnosed to have benign or malignant tumours, the most common being carcinoma of the lung. The median time for detection of T. marneffei by NGS was 2 (range 1-6) days, which is significantly shorter than the median time for detection by fungal culture [7 (range 5-17) days] (P < 0.0001 by Mann-Whitney U test). NGS has emerged as a promising diagnostic tool for T. marneffei infections, especially for picking up cases in HIV-negative patients and rapid diagnosis.

Background: Antifungal susceptibility testing (AFST) guides therapy for invasive and refractory fungal infections, but routine testing of species with predictable, species-level (intrinsic) resistance can waste laboratory resources.

Methods: Narrative synthesis of guideline documents and recent literature to define intrinsic resistance, summarize major fungal examples, and propose a selective AFST framework.

Results: Key taxa show intrinsic non-susceptibility (e.g., Pichia kudriavzevii to fluconazole; Mucorales to short-tailed azoles; Cryptococcus spp. to echinocandins). Terminology differences between EUCAST and CLSI are noted. Recommended AFST is targeted to invasive/rare pathogens, treatment failure, surveillance, outbreak investigation, and evaluation of novel agents.

Conclusion: A selective AFST strategy, reserving routine testing for species with variable or emergent resistance, enhances laboratory efficiency and antifungal stewardship while ensuring appropriate clinical therapy.

The ability to survive and militate oxidative stress has received particular attention as one of the virulence factors of human pathogens. While underlying mechanisms have been largely studied for some fungi, those employed by the rising opportunistic fungal threat Scedosporium spp. are not fully understood yet. Previous transcriptomic studies helped identify the main oxidative stress-induced antioxidant enzymes in S. apiospermum. We therefore wanted to gain insight into regulators governing this response. We aimed to generate and characterize a knock-out mutant of S. apiospermum lacking the SKN7 gene, which encodes one of the main regulators of response to oxidative stress in fungi. The skn7Δ mutant was multifacetedly characterized on phenotypic and transcriptomic levels. Findings support pertinent roles of S. apiospermum Skn7 protein in protection against different types of oxidative stress, mainly cumene hydroperoxide and diamide. Skn7 was also protective against stress-induced accumulation of reactive oxygen species (ROS), as well as macrophage-mediated killing. This protection is likely mediated by the upregulation of genes encoding components of the thioredoxin and peroxiredoxin systems, which exhibit dependency on Skn7. Furthermore, we demonstrated a potential role of Skn7 in the synthesis of the hyphal cell wall. In conclusion, the response regulator Skn7 plays an essential role in protecting S. apiospermum against oxidative threat, whether generated by chemicals or by immune cells. Understanding the regulatory role of fungal Skn7 may help advance therapeutic strategies in combating fungal infections.

Background: Homozygous mutations in the Caspase-associated recruitment domain 9 (CARD9) gene increase susceptibility to invasive fungal infections, particularly those caused by Candida species. This study aims to assess the spectrum of CARD9 gene mutations that predispose individuals in the Turkish population, especially children, to invasive fungal infections.

Methods: Our study included 30 patients who were admitted to Ege University due to invasive fungal infection or chronic mucocutaneous candidiasis between 2020 and 2023. Demographic and clinical data of the patients were recorded, and a sequence analysis of the CARD9 gene was performed.

Results: The median age of the patients was 1.8 years (interquartile range [IQR]: 11.8). Diagnoses included fungal endocarditis (n = 8, 26.6%), chronic mucocutaneous candidiasis (n = 7,23.3%), central nervous system (CNS) infections (n = 6,20%), candidemia (n = 4,13.3%), fungus ball in the kidney (n = 2, 6.7%), endophthalmitis ( n = 1, 3.3%), concurrent CNS and intra-abdominal infection (n = 1, 3.3%), and concurrent CNS infection and endophthalmitis (n = 1, 3.3%). All 12 exons and exon-intron junctions of the CARD9 (NM_052813.5) gene that encodes the CARD9 protein were analyzed. A disease-causing variant was detected in 2 patients (6.6%). One patient had a Pseudallescheria boydii brain abscess, and the other had an invasive fungal infection confirmed histopathologically.

Conclusions: Among the 30 patients with invasive fungal infections, a disease-causing CARD9 mutation was identified in 2 (6.6%) patients. While CARD9 mutations are known to be associated with invasive candidiasis, this study reports the first pediatric case of P. boydii infection associated with a CARD9 mutation.

Sporotrichosis, a globally distributed subcutaneous mycosis, finds its most virulent agent in the species Sporothrix brasiliensis, particularly in zoonotic outbreaks associated with cats. This study investigated the role of aspartic proteases (APs) as potential virulence factors in S. brasiliensis. Through in silico analysis, we identified and characterized 19 genes encoding putative aspartic proteases in the S. brasiliensis genome. Susceptibility assays to different stressors demonstrated distinct profiles between the Sb1168 and Sb5110 strains, but the presence of Pepstatin A strongly inhibited growth under stress, indicating a crucial role for these enzymes in environmental adaptation. Proteolytic activity was modulated by cell wall stressors. Strain Sb1168 showed higher aspartic protease activity (87% inhibition by pepstatin A), while Sb5110 exhibited a mixed enzymatic profile, with significant contributions from metalloproteases (50% inhibition by EDTA and pepstatin A individually, and 80% in combination). Inhibition of APs blocked the mycelium-to-yeast (M → Y) dimorphic transition, suggesting that these proteases are dimorphism regulators. In macrophage assays, APs inhibition resulted in a significant increase in the phagocytic index and a reduction in intracellular fungal viability (CFU count), in addition to altering the profile of secreted cytokines (increase in pro-inflammatory IL-12 and decrease in anti-inflammatory IL-10 in treated Sb1168), suggesting these enzymes modulate immune evasion.

Background: Therapeutic drug monitoring (TDM) of itraconazole (ITC) has been recommended by international guidelines to optimize efficacy and reduce toxicity, especially in the context of invasive fungal infections. However, whether the same therapeutic targets apply to paracoccidioidomycosis (PCM) remains uncertain.

Methods: We conducted a retrospective analysis of patients with proven or probable PCM who used ITC during antifungal treatment between 2016 and 2024 at the University of São Paulo. Two groups were formed: the TDM group and the non-TDM group. Serum samples were obtained at steady-state (≥ 7 days after treatment initiation), and ITC levels were measured by liquid chromatography-mass spectrometry (LC-MS/MS). The institutional standard treatment was ITC capsules at 200 mg once or twice daily, depending on disease severity. Therapeutic serum trough concentrations were defined as 0.5-4.0 mg/L.

Results: Eighty-three patients were included, 18 in the TDM group and 65 in the non-TDM group, predominantly middle-aged males (median age 53 years; 70% male) with the chronic form of PCM (84%). Only 44.4% of initial serum concentrations were within the therapeutic range. Notably, 22% of patients had undetectable serum levels (< 0.014 mg/L). The median ITC concentration was 0.26 mg/L (IQR 0.04-1.95), and no toxic levels were observed. No statistically significant differences were found between the groups regarding ITC dose modification, drug interactions, toxicity, or duration of therapy.

Conclusion: Subtherapeutic serum ITC concentrations were common among PCM patients receiving capsule formulations. Although clinical response was generally favorable, the high variability in absorption highlights the potential value of TDM in selected cases. Prospective studies are warranted to define optimal target levels for PCM management.