IL-24 regulates corneal inflammation and fibrosis in fungal keratitis via the caspase-11/gasdermin D pathway.

Nosocomial invasive Aspergillus calidoustus infection in a CAR-T cell-treated patient with concomitant Aspergillus fumigatus respiratory infection.

The antimicrobial activity of multicomponent, magnetron-sputtered glass coatings was evaluated against phytopathogenic fungi (Botrytis cinerea, Fusarium oxysporum, Cladosporium fulvum, Alternaria solani) and the chromista Phytophthora infestans, with Aspergillus fumigatus included as a model opportunistic pathogen. Fourteen Cu-based multicomponent coatings were deposited on glass using multi-alloy targets composed of Sn, Zn, Al, Ni, Fe, Ti, Mn, Nb, or Co in two high-transmittance variants (≥85% and ≥88%). Antimicrobial activity was assessed in two assays: (A) spore survival after 24–72 h contact, and (B) hyphal growth over 7 days following coating exposure under light and dark conditions. Spore viability decreased after incubation on high-Cu coatings, which showed inhibition for most strains, particularly B. cinerea, F. oxysporum, and P. infestans. The effects on spore germination were independent of the direct transmittance value of the coated glass. Hyphal growth was generally less affected by a high Cu content for most strains. Hyphal growth of F. oxysporum, C. fulvum, A. solani and B. cinerea was reduced by up to 30% on selected multicomponent coatings. For most strains, hyphal growth showed no inhibition after light incubation on coatings. However, light-dependent effects were observed for A. solani, A. fumigatus and P. infestans, while B. cinerea and C. fulvum showed reduced sensitivity during the first two days. High-Cu coatings were most effective at inhibiting spore germination, whereas hyphal growth on multicomponent coatings may respond to different ions. Therefore, high-Cu, two-component coatings may be recommended for practical greenhouse applications.

Development and application of a rapid detection system for Aspergillus fumigatus based on ERA/CRISPR-Cas12a.

Paracoccidioidomycosis (PCM) is a systemic infection that is endemic to Latin America, caused by thermodimorphic fungi from the Paracoccidioides genus. These fungi are facultative intracellular parasites of macrophages. LC3-associated phagocytosis (LAP), a non-canonical form of autophagy, plays a critical role in the response of these phagocytes to similar pathogens. In this study, we investigated the role of LAP in the macrophage responses to Paracoccidioides spp. We detected LAP in macrophages infected with Paracoccidioides spp by immunofluorescence microscopy with antibodies to LC3. Piceatannol and diphenyleneiodonium chloride (DPI), respectively Syk and nicotinamide adenine dinucleotide phosphate oxidase (NADPH) inhibitors, were used to understand the role their pathways played. To determine the function of LAP, we targeted ATG5, a key autophagy gene, by RNA interference. We observed LC3 recruitment to phagosomes containing Paracoccidioides spp. in RAW264.7 and J774.16 cell lines and in bone marrow-derived macrophages. ATG5 RNA interference reduced the antifungal activity of J774.16 cells, highlighting the importance of LC3 recruitment for effective fungal control. Interestingly, pharmacological inhibition of Syk kinase and NADPH oxidase pathways, essential for LAP against Aspergillus fumigatus and Candida albicans, did not impair LAP against P. brasiliensis. This suggests distinct triggering mechanisms, possibly due to differences in the fungal cell surface composition. These findings suggest that LAP plays a significant role in the host defense against Paracoccidioides spp. and may represent a promising target for host-directed PCM therapies.

This article describes the experiments with the two investigated fungal strains isolated from soils on Livingston Island, Antarctica. Our studies by gas chromatography - mass spectrometry (GC - MS) analyses showed the ability degree of the strains to degrade low molecular weight polyaromatic compounds such as naphthalene and phenanthrene. The different degradation capacity of both strains towards each one of the compounds studied was established. The amount of naphthalene in the medium decreased by 44 % during the 9 days cultivation of Aspergillus fumigatus AL3, while it decreased by 37 % when grown in a medium inoculated with Aspergillus fumigatus AL9. The strain A. fumigatus AL3 was able to reduce the phenanthrene amount in the medium by 44.5 %, whereas A. fumigatus AL9 reduced it by a significant 90.5 % under the same conditions and the same period. Some of the intermediates, suchas naphthalene - 1, 2 - diol, 2 - hydroxybenzaldehyde, 2 - hydroxybenzoic acid, naphthalene - 1 - ol, benzene - 1, 2 - dicarboxylic acid, and benzene - 1, 2 - diol, in the catabolite chain of both compounds were also identified. They are typical for the biodegradation of the investigated compounds also with the help of other types of microorganisms.

The innate immune response to A. fumigatus in alveolar macrophages: Roles of LC3-associated phagocytosis, apoptosis and inflammation.

Using DNA metabarcoding to monitor key factors affecting the fungal community in Licorice: collection site, processing method, and storage condition.

Abstract Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of immune dysregulation that may be triggered or exacerbated by infections, malignancy, autoimmune disease, or iatrogenic immunosuppression. In rheumatologic conditions such as adult-onset Still's disease (AOSD), HLH can manifest as macrophage activation syndrome (MAS), a related hyperinflammatory state. Opportunistic infections, particularly with intracellular pathogens such as Mycobacterium avium complex (MAC), can mimic or precipitate HLH, creating diagnostic and therapeutic dilemmas. Methods: We report the case of a 40-year-old woman with AOSD complicated by recurrent MAS who developed disseminated opportunistic infections while on prolonged immunosuppressive therapy, including anti–interferon-gamma (IFN-γ) monoclonal antibody. Clinical, radiologic, microbiologic, and pathologic findings were reviewed in detail along with focused literature review on disseminated nontuberculous mycobacterial (NTM) infections in non-HIV immunocompromised patients with HLH or MAS, emphasizing risk factors, diagnostic approaches, and management considerations. Results: The patient was admitted with fever, cytopenias, and ulcerated skin lesions. Imaging demonstrated disseminated infection involving the lungs, liver, brain, lymph nodes, and soft tissues. Karius microbial cell-free DNA testing identified MAC, Mycobacteroides abscessus , Aspergillus fumigatus , and Verruconis gallopava . Histopathology revealed acid-fast bacilli (AFB)–positive infiltrates in skin and bone marrow. She subsequently developed fungal endophthalmitis and tricuspid valve endocarditis. Despite broad-spectrum antimicrobials and intensive care, she experienced progressive multiorgan failure and died. Postmortem examination confirmed disseminated MAC and V. gallopava , with extensive hemophagocytosis. Immunologic testing did not identify a primary immunodeficiency, though hypogammaglobulinemia and prolonged immunosuppression suggested profound acquired immune dysfunction. Discussion: This case illustrates the complex interplay between HLH, immunosuppressive therapy, and opportunistic infection. IFN-γ blockade may impair host defenses against intracellular organisms such as MAC, whereas HLH-directed treatments further increase infectious risk. Functional immune testing may help identify patients at risk for opportunistic infections. Recognizing iatrogenic and secondary immunodeficiencies in HLH is crucial for optimizing management and improving outcomes in this high-risk population.

Aspergillus fumigatus is a significant pathogen responsible for a wide spectrum of pulmonary diseases, ranging from allergic reactions to invasive pulmonary aspergillosis, particularly among immunocompromised individuals. We describe a 62-year-old female kidney transplant recipient who presented with chest pain, a right anterior chest wall mass, cough and anorexia of 2 months' duration. Laboratory evaluation revealed elevated inflammatory markers, prompting consideration of malignancy and infection. Bronchoalveolar lavage was positive for Aspergillus galactomannan antigen, and biopsy of the chest wall mass confirmed Aspergillus infection. This case represents an unusual manifestation of Aspergillus involving soft tissue. Accurate diagnosis requires histopathological confirmation and molecular testing. This report emphasizes the importance of including fungal infections, particularly Aspergillus species, in the differential diagnosis of soft tissue masses in immunocompromised patients.

Invasive Aspergillus tracheobronchitis (IATB) is a rare but potentially fatal manifestation of invasive aspergillosis. Because of its high mortality, prompt recognition and initiation of antifungal therapy are crucial. We report the case of a 71-year-old woman with a history of diffuse large B-cell lymphoma (DLBCL) who presented with progressive dyspnea. Computed tomography revealed subglottic airway stenosis, necessitating an emergency tracheostomy to secure the airway. Histopathological and microbiological examination of bronchoscopic biopsy specimens demonstrated infiltration of Aspergillus fumigatus, establishing the diagnosis of IATB. Antifungal therapy with voriconazole was promptly initiated, resulting in gradual clinical and endoscopic improvement. The tracheostomy tube was successfully removed, and the airway lesion showed complete resolution. This case underscores the importance of early diagnosis and timely antifungal therapy to achieve a favourable outcome. When severe airway obstruction is present, airway interventions such as tracheostomy may be lifesaving.

Allergic bronchopulmonary aspergillosis (ABPA) is arare but potentially severe hypersensitivity reaction to Aspergillus fumigatus, primarily affecting patients with asthma or cystic fibrosis. Early diagnosis is crucial to prevent irreversible lung damage. High-resolution computed tomography (HRCT) is the standard imaging method for detecting bronchiectasis and other typical findings. Common features include central, saccular bronchiectasis, mucus impaction, and centrilobular micronodules. Radiological assessment must be closely integrated with clinical and laboratory parameters. The revised 2024 International Society for Human and Animal Mycology (ISHAM) criteria further emphasize the diagnostic importance of radiological features. High-attenuation mucus (HAM) is considered ahighly specific finding and may confirm the diagnosis. Modern classification systems allow more precise disease staging. HRCT provides extremely high sensitivity for the radiological hallmarks of ABPA. Detection of HAM is regarded as nearly pathognomonic. Fleeting infiltrates and reversible changes are reliably visualized. Correlating radiological findings with laboratory parameters significantly improves diagnostic accuracy. HRCT remains the indispensable imaging modality for diagnosing and monitoring ABPA. In cases of clinical suspicion, early HRCT of the thorax should be performed. A combination of radiological findings and serological criteria is recommended to confirm the diagnosis. HRCT can be used to detect reversible infiltrates and assess response to treatment.

This study focused on optimizing endoglucanase production using a peculiar fungal co-culture comprising Rhizopus arrhizus and Aspergillus fumigatus, identified through morphological and 18S rDNA analyses. The co-culture achieved the highest enzyme production after 72 h of fermentation with alkaline-treated substrates. Scanning Electron Microscopy (SEM) revealed substantial structural disruption in pretreated biomass, enhancing enzyme accessibility. Among the tested substrates, pea hulls proved to be the most effective for enzyme production. Optimization of physical and nutritional parameters was performed using Design of Experiments (DOE) approaches, specifically Plackett-Burman Design (PBD) for screening and Central Composite Design (CCD) for fine optimization. The maximum endoglucanase activity of 119.58 U/mL/min was obtained under the optimized conditions of 27.5 °C, pH 5.5, inoculum age 3.5 days, and supplementation with 1.5% fructose, 1.25% yeast extract, 1.25% sodium nitrate, and 1.25% Tween 80. Analysis of Variance (ANOVA) confirmed the significance of these parameters and their interactions at a 95% confidence level, with a strong model fit (R2 = 0.9052). This study demonstrates the potential of waste pea hulls as a cost-effective substrate for enzyme production, supporting waste valorization and contributing to a circular bioeconomy through sustainable biomass utilization.

Recurrent wound complications after cardiac surgery are usually associated with deep sternal wound infections. We report a rare case of a patient with persistent wound complications and no clear evidence of deep sternal infection, who was eventually diagnosed with fungal osteitis and successfully treated with free tissue transfer. A 66-year-old man with multiple comorbidities underwent off-pump coronary artery bypass grafting using the left internal thoracic artery as a conduit. Three months after surgery, the patient developed persistent wound complications at the sternotomy site. Despite repeated debridement, the wound failed to heal, and cultures remained negative for several months. Eventually, Aspergillus fumigatus was identified, and invasive fungal osteitis was confirmed histologically. After serial debridement, definitive reconstruction was performed using a free latissimus dorsi musculocutaneous flap. The right internal thoracic artery and vein served as recipient vessels, ensuring dead space obliteration and stable chest wall coverage. The patient recovered without further wound complications, and long-term antifungal therapy was maintained. At follow-up, no evidence of recurrent infection was observed. This case highlights the clinical challenges posed by fungal osteitis, a rare but difficult-to-treat condition.

An automated medium-pressure liquid chromatography (MPLC) system was employed for the preparative-scale isolation of lupane-type triterpenoids from Glochidion zeylanicum var. tomentosum (Dalzell) Trimen. Seven compounds were isolated and identified as glochidone (1), glochidonol (2), glochidiol (3), lupeol (4), epilupeol (5), lup-20(29)-ene-3α,23-diol (6) and lup-20(29)-ene-1α,3β-diol (7). The antimicrobial activity of these compounds was evaluated against Micrococcus luteus, Staphylococcus aureus, Aspergillus fumigatus and Rhizopus oryzae using the minimum inhibitory concentration (MIC) method. Glochidiol (3) showed moderate activity against S. aureus (64 µg/mL) and R. oryzae (32 µg/mL). Compound 6 also showed moderate antifungal activity against A. fumigatus (64 µg/mL). The results highlight the efficiency of MPLC and the influence of hydroxyl substitution on antimicrobial activity.

Tobacco is rich in natural bioactive compounds, yet the antifungal potential of its essential oil remains largely unexplored. In this study, we demonstrate for the first time that tobacco essential oil exhibits significant antifungal activity against the opportunistic human pathogen Aspergillus fumigatus. At high concentrations, the oil effectively inhibits hyphal growth and suppresses conidial production. Chemical profiling identified nootkatone as the principal active compound. Nootkatone exerts a concentration-dependent dual antifungal effect, simultaneously inhibiting hyphal elongation and spore formation. Mechanistic analyses revealed that the calcium signaling pathway, particularly the crzA and cchA genes, plays a central regulatory role in mediating fungal resistance to nootkatone. Deletion of either gene (ΔcrzA or ΔcchA) led to significantly increased sensitivity to nootkatone, highlighting their role in nootkatone stress response. Furthermore, under nootkatone stress, CrzA was found to regulate the expression of multiple efflux pump genes (abcC, abcE, atrA, mdr1, and atrB), uncovering a previously unrecognized link between calcium signaling and nootkatone efflux. In addition to targeting cellular signaling, nootkatone also disrupted fungal cell wall integrity and triggered the release of host immune mediators, suggesting a synergistic antifungal mechanism that combines structural disruption with immune activation. In the Galleria mellonella infection model, nootkatone significantly enhanced host survival and reduced fungal burden. Notably, treatment of ΔcrzA-infected larvae resulted in a 70% survival rate, markedly higher than that observed in wild-type (WT) infections. Moreover, nootkatone retained strong inhibitory activity against itraconazole-resistant isolates, underscoring its potential as a novel, broad-spectrum antifungal agent. KEY POINTS: • Nootkatone inhibits fungal growth-suppresses Aspergillus fumigatus hyphae and spores via dual concentration-dependent action • Targets calcium signaling-key genes (crzA/cchA) regulate resistance; deletion enhances susceptibility and links to efflux pump activation. • Dual antifungal mechanisms and drug resistance overcoming-disrupts cell wall integrity, activates host immunity, and is effective against azole-resistant strains, boosting survival in infection models.

Gliotoxin of Aspergillus fumigatus has been extensively studied for its role in pathogenesis in animals and humans. It triggers pathogenesis by its immunosuppressive and cytotoxic effects. Biosynthetic gene cluster (BGC) consisting of 13 genes regulates its biosynthesis. We targeted gliZ, gliP and gliA genes of this BGC using CRISPR/Cas9 system in a multigene editing approach to check the pathogenesis in broilers. crRNAs were designed using EuPaGDT and 3 single guide RNAs (sgRNA) were commercially synthesized. Each sgRNA was combined with Cas9 to form ribonucleoprotein complexes which were then used for simultaneously transfecting fungal protoplasts. Thin-layer chromatography showed the absence of gliotoxin on silica plate and DNA sequencing showed various indels in target genes. These indels caused amino acid substitutions in all three gene products but, the gliP mutation, since it was synonymous, was likely not functionally relevant. Regenerated protoplasts were matured to form fungal hyphae and spore production was induced. These spores were inoculated intra-air sac in broiler chicks. During one-week infection trial, birds infected with the wild-type spores (group 1) showed morbidity and their mortality rate was 30%. Birds inoculated with RNP-treated spores (group 2) showed mild clinical signs and no mortality. No morbidity or mortality was recorded in birds in negative control group (group 3). Histopathological analysis of lungs showed necrosis and congestion, and presence of mixed population of inflammatory cells in wild-type infected birds, while no such lesions were seen in birds infected with RNP-treated spores. These results show that multigene editing approach was successful in creating indels simultaneously in 3 gliotoxin genes which resulted in amino acid substitution which negatively impacted gliotoxin biosynthesis and export. In vivo experiment results show that RNP-treated fungal spores were unable to cause A. fumigatus pathogenicity in broiler. Targeting gliotoxin biosynthesis could thus be a promising approach to develop antifungal therapy.

A BSTRACT Background: Aspergillus sensitization is increasingly recognized as a key factor in atopic diseases. This study aimed to measure the incidence of Aspergillus skin prick test (SPT) positivity among patients with atopic and nonatopic symptoms visiting a tertiary care center. Materials and Methods: This hospital-based, analytical cross-sectional study was conducted over 18 months at a tertiary care hospital. A total of 190 patients were enrolled using consecutive sampling and categorized into symptomatic (atopic) and asymptomatic (nonatopic) groups. SPTs for various Aspergillus species were performed, along with clinical evaluations. Moreover, absolute eosinophil count (AEC) and serum immunoglobulin E (IgE) levels were analyzed. Statistical comparisons were made using Chi-square tests and binary logistic regression. Results: The incidence of Aspergillus SPT positivity was significantly higher in symptomatic patients (atopic) (55.8%) including expectoration, chest tightness, allergic rhinitis (AR), eczema, wheezing, AEC positivity, and total serum IgE compared to asymptomatic patients (nonatopic) (10.5%). Allergens from Aspergillus species, such as Aspergillus fumigatus , Aspergillus flavus , and Penicillium spp., were more prevalent among symptomatic patients ( P < 0.01). Elevated AEC and serum IgE levels were strongly associated with Aspergillus positivity. Multivariate analysis identified chest tightness, dyspnea, AR, and smoking as significant predictors of Aspergillus sensitization. Furthermore, moderate disease severity was the most common presentation among Aspergillus -positive individuals. Conclusion: The study underscores the significant association of Aspergillus sensitization with atopic symptoms and disease severity. These findings emphasize the importance of early allergen identification and targeted management in atopic patients to mitigate disease progression and improve quality of life.

The antifungal activity of 2-Amino-5-(3-nitrophenyl)-1,3,4-thiadiazole is investigated against Aspergillus niger using combined experimental and computational approaches. The compound is synthesized via a one-step cyclization reaction and structurally characterized using FT-IR and ¹H NMR spectroscopy, confirming its chemical integrity. In vitro agar well-diffusion assays demonstrated significant, concentration-dependent inhibition of fungal growth, with the highest activity observed at 5000 µg/mL. Density Functional Theory (DFT) calculations revealed a HOMO–LUMO gap of 3.709 eV and intramolecular charge transfer characteristics, suggesting electronic stability and reactivity. Homology modeling of A. niger sterol 14-α-demethylase (CYP51) is performed using CYP51B from Aspergillus fumigatus (PDB ID: 6CR2) as the template, and model validation using MolProbity and QMEANDisCo confirmed high stereochemical quality. Molecular docking showed favorable binding interactions of the compound within the heme-containing active site, while QSAR analysis further supported structure-activity relationships correlating molecular features with antifungal potency. Collectively, these results highlight 2-Amino-5-(3-nitrophenyl)-1,3,4-thiadiazole as a promising lead for antifungal drug development against A. niger. From a nanotechnology perspective, the molecular size, electronic structure, and surface-interaction capability of 2-Amino-5-(3-nitrophenyl)-1,3,4-thiadiazole suggest its suitability for incorporation into nano-enabled antifungal systems. The compound’s favorable electronic properties, strong binding affinity to CYP51, and concentration-dependent biological activity support its potential use in nanoparticle-based delivery platforms or nano-structured coatings aimed at enhancing antifungal efficacy and selectivity. These findings highlight the relevance of the present study for the rational design of nanotechnology-driven antifungal therapeutics.

This article reports a rare pediatric case of allergic bronchopulmonary aspergillosis (ABPA) complicated by concurrent pinworm infection, highlighting immune interaction and individualized, stepwise management. A 10-year-7-month-old girl presented with recurrent cough and wheezing; laboratory testing showed marked eosinophilia (1.23×109/L) and elevated total immunoglobulin E (1 196 IU/mL). Aspergillus fumigatus IgG was 88.61 AU/mL, and Aspergillus fumigatus allergen m3-specific IgE was 0.37 IU/mL. Stool parasite examination confirmed pinworm infection. Chest computed tomography demonstrated atypical segmental pulmonary consolidation. Through multidisciplinary collaboration, stepwise anti-infective therapy (cefoperazone-sulbactam followed by imipenem and then voriconazole), pulsed anthelminthic therapy (albendazole), and immunomodulatory treatment were implemented, resulting in complete symptom resolution and sustained remission over 30 months of follow-up. This case illustrates a dynamic balance of Th2 immune polarization under parasitic-fungal co-infection and, for the first time, proposes a "parasite-fungus-immune memory triangle" conceptual model, offering insights for individualized management in complex pediatric infections.