Chromoblastomycosis is a chronic implantation mycosis caused by melanized fungi, typically affecting rural male workers following traumatic inoculation with soil or vegetative matter. It most commonly involves the lower limbs and is often diagnosed late because of its indolent course and its resemblance to other chronic verrucous dermatoses. We report the case of a 54-year-old man who presented with a 10-year history of a slowly progressive lesion involving the right hand and distal forearm. The lesion was associated with intermittent pruritus and occasional serous discharge. Clinically, the large plaque over the hand and forearm resembled lupus vulgaris, creating diagnostic difficulty. Histopathology, however, demonstrated characteristic sclerotic bodies, establishing the diagnosis of chromoblastomycosis. The case is notable for the unusual upper-limb involvement, large lesion size, and clinical resemblance to lupus vulgaris. This report highlights the importance of considering chromoblastomycosis in the differential diagnosis of long-standing plaques over exposed upper extremities.

Fungal skin infections represent the fourth most prevalent disease globally, predominantly attributed to dermatophyte species such as Trichophyton. Nevertheless, sporadic instances of dermatophytosis may also arise from opportunistic, uncommon fungi. This study documents the association of keratinophilic fungi, Myriodontium keratinophilum and Aphanoascus verrucosus, with cases of dermatophytosis in Kashmir, North India. Internal transcribed spacer region sequencing of 64 isolates obtained from skin, hair, and nail samples of 62 patients identified 61% of isolates (n = 39) as M. keratinophilum, followed by Trichophyton indotineae and A. verrucosus in 20% (n = 13) and 19% (n = 12) cases, respectively. Furthermore, the first hybrid de novo genome assembly of M. keratinophilum is reported in the present study. Genomic analysis of both M. keratinophilum and A. verrucosus species revealed median intra-species single nucleotide polymorphism (SNP) differences of 100 and 27, respectively, suggesting highly related strains in the patient population. De novo functional annotation identified a higher number of coding regions in M. keratinophilum compared to T. indotineae and A. verrucosus, including carbohydrate-active enzymes (CAZymes) exhibiting unique substrate affinities and subtilisin 3 (SUB3) gene, previously implicated as a potential virulence gene in dermatophytes. Notably, in addition to all the multidrug transporters encoded by Trichophyton species, M. keratinophilum genome contains six putative ATP-binding cassette (ABC) transporters showing 40%-70% sequence similarity with the CDR1 gene. M. keratinophilum exhibited reduced susceptibility to multiple antifungals, including high minimum inhibitory concentrations (MICs) (>16 mg/L) against griseofulvin and itraconazole. Importantly, itraconazole is a primary therapeutic agent for terbinafine-resistant T. indotineae infections, underscoring the necessity for early and accurate identification and intervention of dermatophytic infections.IMPORTANCEThe study reports cases of dermatophytosis associated with two rare keratinophilic fungi, i.e., Myriodontium keratinophilum and Aphanoascus verrucosus. The cases mainly presented as tinea corporis and cruris, commonly caused by Trichophyton indotineae in the Indian subcontinent, which may remain undiagnosed due to a lack of molecular identification. Furthermore, the first-ever genome report of M. keratinophilum and its ab initio functional annotation is useful for further studies and management of opportunistic pathogens that exhibit reduced susceptibility towards itraconazole, the first-line drug of treatment for terbinafine-resistant T. indotineae infections. An early correct molecular identification of the etiologic agents of skin infections is warranted to tackle the new agents of dermatophytosis at the earliest stage.

In the treatment of e.g. infectious diseases, administration of multiple drugs over extended periods is common. Long-acting injectables improve patient compliance, and combining multiple drug compounds into a single suspension may provide additional benefits. This study investigated the physical stability of dual-drug co-suspensions prepared by wet bead milling, with particular focus on stabiliser selection and concentration. In total, nine stabilisers were screened in combination with itraconazole and carbamazepine as individual suspensions and in co-suspensions, followed by evaluation of selected stabilisers using the cinnarizine-itraconazole system and concentration optimisation for the carbamazepine-itraconazole system. Physical stability was assessed by laser diffraction over 28 days of storage at 40°C. Poloxamer 338 generally provided the best performance for itraconazole-containing suspensions, whereas PVP K30 was most effective for carbamazepine, despite foaming challenges. The particle size of carbamazepine-itraconazole co-suspensions generally followed the trends observed for itraconazole suspensions, whereas the change in particle size during storage did not directly reflect either individual suspension. Interestingly, several co-suspensions produced smaller particles than the corresponding single-drug suspensions. Increasing stabiliser concentration either enhanced or reduced milling efficiency depending on the formulation, and the concentration providing the greatest particle size reduction did not consistently provide the optimal physical stability. These findings demonstrate that although particle size characteristics of co-suspensions may follow the trends observed for one corresponding single-drug suspension, their physical stability cannot be predicted solely from the individual suspensions.

Aspergillus section Nigri is distributed ubiquitously in nature and is reported to be the third most clinically significant species of the Aspergillus genus. In this study, we surveyed Aspergillus section Nigri isolates from Zhongshan Hospital, Fudan University, Shanghai, China, from 2019 to 2023. We determined the species distribution of section Nigri isolates by partial β-tubulin gene sequencing. We characterized the antifungal susceptibility profiles of these isolates to medical azoles (itraconazole, voriconazole, posaconazole, and isavuconazole) using the Sensititre[TM] custom-designed broth microdilution system. The cyp51A sequences were compared between azole-resistant and azole-susceptible strains in order to determine the potential antifungal resistance mechanism. A total of 54 Aspergillus section Nigri isolates were obtained. A. tubingensis (50.0%) and A. niger (46.3%) were the most prevalent species. Two isolates of A. welwitschiae were identified. Resistance to Itraconazole, voriconazole, and isavuconazole was found in 26%, 33.3%, and 33.3% of A. tubingensis isolates, respectively. All A. niger and A. welwitschiae isolates were sensitive to these azoles. Three amino acid mutations were found in azole-resistant A. tubingensis isolates, namely Y119F, Y119H, and T321A. Results from this study provide us with an understanding of species distribution and antifungal susceptibility profiles of clinical Aspergillus section Nigri isolates in Eastern China. It highlights the importance of accurate species identification and antifungal susceptibility testing. Our results also suggest that the novel Y119F substitution is potentially a key player in azole resistance.

Reliable endogenous biomarkers for assessing CYP3A activity and clinical drug-drug interaction (DDI) risk remain limited. We characterized global metabolomic changes following itraconazole treatment in a fixed-sequence DDI study (11 healthy volunteers) to identify novel CYP3A endogenous biomarkers. Untargeted metabolomic analysis identified 58 plasma metabolites that were significantly modulated (changed by > 1.5-fold or < 0.67-fold, P < 0.05), highlighting the dynamic and systemic impact of CYP3A inhibition on the human metabolome. Bile acids represented the most prominently affected analytes, whereas changes were also observed in endocannabinoids, xanthine metabolism, and food-derived metabolites, revealing both on-target and potential off-target effects of itraconazole. For example, plasma levels of endocannabinoidome metabolites such as linoleoyl ethanolamide and N-linoleoylglycine increased by 2.4- to 6.0-fold (P < 0.05), while bile acids including glycoursodeoxycholate (GUDCA) and glycohyocholate (GHCA) decreased by 2.6- to 12.5-fold (P < 0.01) following itraconazole treatment. Targeted quantification was subsequently performed for the bile acids identified from untargeted analysis and the emerging CYP3A biomarkers, 1β-hydroxy-deoxycholic acid (1βOH-DCA) and its glycine and taurine conjugates. Notably, GHCA, GUDCA and 1βOH-DCA conjugates exhibited pronounced reduction in plasma exposure (~10-fold, P < 0.001) in the itraconazole treatment group. GHCA exhibited lower inter-individual variability than others. In vitro characterization demonstrated CYP3A4-selective hydroxylation of glycochenodeoxycholate to form GHCA, supporting its mechanistic linkage to CYP3A4 activity. Collectively, these findings expand the repertoire of sensitive and mechanistically supported endogenous biomarkers of CYP3A activity. Further evaluation of the newly identified GHCA and emerging bile acid metabolites across diverse CYP3A inhibitors can strengthen their translational utility in DDI risk assessment and drug development.

Candida tropicalis is an important opportunistic yeast increasingly associated with antifungal resistance across different ecological contexts. We systematically reviewed research articles published up to June 1, 2026, to investigate the distribution of C. tropicalis in non-clinical niches and synthesize evidence on its susceptibility to clinically relevant antifungals and agricultural fungicides, virulence-associated traits, and resistance-related genes. Database searches were conducted in PubMed, Web of Science, ScienceDirect, Google Scholar, Scopus, and SciELO. A total of 35 eligible studies were included, comprising 1011 C. tropicalis isolates. Most isolates originated from environmental sources (694/1011; 68.6%), mainly soil (159/694; 22.9%) and beach sand (124/694; 17.9%), whereas 317/1011 (31.4%) were recovered from animal sources. Across all studies, 769 antifungal resistance or reduced-susceptibility events were identified, including 422 (54.9%) among environmental isolates and 347 (45.1%) among animal-derived isolates. Resistance was predominantly associated with azole antifungals, particularly fluconazole (FLC) (358/1008; 35.5%; 95% CI: 32.6-38.5%), followed by itraconazole (ITZ) (116/511; 22.7%; 95% CI: 19.3-26.5%) and voriconazole (VOR) (98/418; 23.4%; 95% CI: 19.6-27.7%). Evidence of cross-resistance between clinical azoles and agricultural fungicides was reported in six of the seven studies evaluating both compound classes. Furthermore, isolates frequently exhibited virulence-associated phenotypes, including strong biofilm formation (94/130; 72.3%; 95% CI: 64.1-79.3%) and strong hemolytic activity (48/80; 60.0%; 95% CI: 49.0-70.0%). Molecular analyses identified recurrent ERG11 mutations and the overexpression of efflux pump-related genes, which are also recognized as major resistance mechanisms in clinical C. tropicalis isolates. Collectively, these findings demonstrate that environmental and animal-derived C. tropicalis isolates frequently exhibit azole resistance, including cross-resistance to agricultural fungicides, together with virulence-associated phenotypes and resistance-related genetic mechanisms consistent with those reported in clinical isolates - underscoring the role of these reservoirs in the maintenance and dissemination of resistant and virulent lineages within a One Health framework.

Carriers of the fragile X messenger ribonucleoprotein 1 (FMR1) gene have an elevated risk of developing Fragile X-associated tremor/ataxia syndrome (FXTAS), a progressive late-onset neurodegenerative disorder. Expansion of CGG trinucleotide repeats within the 5' untranslated region leads to RNA-mediated toxicity and promotes the aggregation of toxic FMR1polyglycine (FMR1polyG), driving neuronal dysfunction and degeneration. Yet, effective therapies that alter disease progression remain lacking. In this study, we evaluated a drug repurposing strategy to modulate FXTAS pathogenesis by targeting CGG repeat RNA structures using Itraconazole (ITZ), a clinically approved antifungal, in combination with Lacosamide (LCM), an established antiepileptic drug. The ITZ+LCM combination significantly reduced FMR1polyG aggregation and attenuated oxidative stress and cell death in an in vivoDrosophila model of FXTAS. Notably, this combination also improved locomotor performance and extended the lifespan of model flies, with a fourfold reduction in the effective ITZ dose. These findings were further validated at the cellular level using (CGG)99 transfected HEK293T and COS-7 cells, wherein the ITZ+LCM treatment suppressed FMR1polyG aggregation and corrected CGG repeat splicing defects. Biophysical studies revealed the selective interaction of the drug combination with CGG-expanded RNA. These findings identify the ITZ+LCM combination as a promising, clinically translatable therapeutic strategy against FXTAS to counter RNA-mediated neurotoxicity.

Introduction: Gastrointestinal basidiobolomycosis is an uncommon invasive fungal infection caused by Basidiobolus ranarum, an environmental mould endemic to the arid south-west of Saudi Arabia and to a handful of other hot, dry regions. Its non-specific presentation routinely invites misdiagnosis as inflammatory bowel disease, tuberculosis or malignancy, and extension to the biliary tree is decidedly rare. Case Presentation: We report a 25-year-old Saudi woman who developed chronic watery diarrhoea and pronounced weight loss two months after her first delivery. Severe microcytic anaemia, leukocytosis, a very high erythrocyte sedimentation rate and multisegmental colonic wall thickening were initially attributed to inflammatory bowel disease complicated by Clostridioides difficile colitis. She subsequently required cholecystectomy for acalculous cholecystitis and then deteriorated, with gastric outlet obstruction and collections at the gallbladder bed. Re-examination of the gallbladder specimen revealed broad, pauci-septate hyphae enveloped by the Splendore-Hoeppli phenomenon, and culture yielded an isolate phenotypically identified as B. ranarum. Voriconazole followed by itraconazole achieved near-complete clinical and radiological recovery. Discussion: We hypothesise that the early puerperium could represent a possible, though as yet unproven, window of susceptibility to this infection. Conclusions: In endemic regions, gastrointestinal basidiobolomycosis should be considered when presumed inflammatory bowel disease behaves atypically; deep tissue sampling is often decisive, and prolonged triazole therapy can achieve an excellent outcome.

Gastric involvement with Histoplasma capsulatum infection is rare but can mimic peptic ulcers or cancer, delaying diagnosis. A 71-year-old man presented with oral ulcer, abdominal pain, and weight loss. The patient had history of tonsillar histoplasmosis treated 8 years before the current presentation with confirmed resolution. The patient had no history of malignancy, autoimmune diseases, or recent travel. Initial laboratory evaluation revealed normocytic anemia. Imaging did not show acute abnormalities that would account for his symptoms. Esophagogastroduodenoscopy revealed multiple gastric ulcers. Biopsies showed chronic gastritis with ulceration and fungal yeasts consistent with H. capsulatum. Similarly, the oral ulcer showed non-necrotizing granulomas with fungal forms. Itraconazole was initiated and follow-up esophagogastroduodenoscopy showed healing ulcers.

Sporotrichosis, a subcutaneous mycosis caused by dimorphic fungi of the Sporothrix genus, has become a major zoonotic epidemic in South America, primarily driven by Sporothrix brasiliensis. To elucidate the genomic basis of its emergence and antifungal adaptation, we analyzed whole-genome sequences from 95 Sporothrix isolates, integrating single-nucleotide polymorphism (SNP), copy number variation (CNV), and genome-wide association (GWAS) analyses. Comparative genomics revealed 610,242 SNPs within S. brasiliensis and 1,474,627 within S. schenckii, confirming a marked disparity in intraspecific diversity. Phylogenomic tree inference resolved six well-supported S. brasiliensis clades with limited internal divergence, reflecting recent population expansion, while S. schenckii displayed deep phylogeographic structure separating North and South American lineages. CNV profiling identified 158 affected genes in S. brasiliensis (60 gains, 98 losses) and 88 in S. schenckii (54 gains, 34 losses), concentrated near sub-telomeric regions. In S. brasiliensis, gains were enriched for kinases and intracellular trafficking functions, whereas losses involved genes related to translation and primary metabolism, suggesting regulatory reinforcement coupled with metabolic streamlining. A GWAS of itraconazole resistance identified 81 SNPs distributed across multiple scaffolds, with many located within genes related with transport, signaling, and redox balance, supporting a polygenic basis for azole response. The implication of these alleles with itraconazole resistance warrants experimental followup. Together, these results highlight distinct evolutionary strategies of closely related Sporothrix species and pinpoint genomic changes potentially associated with the emergence and drug tolerance of S. brasiliensis.