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Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions.

Aspergillus terreus has attracted interest due to its application in industrial biotechnology, particularly for the production of itaconic acid and bioactive secondary metabolites. As related species also seem to possess a prosperous secondary metabolism, they are of high interest for genome mining and exploitation. Here, we present draft genome sequences for six species from Aspergillus section Terrei and one species from Aspergillus section Nidulantes. Whole-genome phylogeny confirmed that section Terrei is monophyletic. Genome analyses identified between 70 and 108 key secondary metabolism genes in each of the genomes of section Terrei, the highest rate found in the genus Aspergillus so far. The respective enzymes fall into 167 distinct families with most of them corresponding to potentially unique compounds or compound families. Moreover, 53% of the families were only found in a single species, which supports the suitability of species from section Terrei for further genome mining. Intriguingly, this analysis, combined with heterologous gene expression and metabolite identification, suggested that species from section Terrei use a strategy for UV protection different to other species from the genus Aspergillus. Section Terrei contains a complete plant polysaccharide degrading potential and an even higher cellulolytic potential than other Aspergilli, possibly facilitating additional applications for these species in biotechnology.

Marine fungi are promising sources of bioactive natural products. The harsh marine conditions favour the production of natural products with unique structures and functions. The different classes of bioactive metabolites produced by these marine fungi can exhibit cytotoxic, apoptotic, anti-proliferative, antiangiogenic, and autophagy inducing effects on a plethora of cancer cell lines. This review, based on research articles that have been published from 2002 to 2023, provides a concise overview of the anticancer properties of metabolites from marine Aspergillus fungal species. A total of 204 papers are reviewed and 208 most active cytotoxic molecules are reported from Aspergillus. The source as well as the growth medium utilised for the production of cytotoxic metabolites are listed. The mechanism of action of some compounds, which could be used as potential drugs, is also reported. These fungi, under optimal growth conditions, have immense potential as anticancer agents, produce novel metabolites with specific structures that can kill a panel of human cancer cells. However, there is a dire need for more clinical trials and understanding of the mechanisms of action of pharmacologically active constituent. Research should also target how to improve culture methods and perform clinical research on human subjects with more scientific reproducibility. [ABSTRACT FROM AUTHOR]

Primary cutaneous aspergillosis (PCA) is a rare opportunistic infection caused by Aspergillus that can be life‐threatening. PCA is mainly reported in immunocompromised hosts such as patients with AIDS, those with hematologic malignancy, or infants with occlusive dressings. However, no study has previously reported PCA associated with toxic epidermal necrolysis (TEN). This study reports four cases of TEN complicated with PCA, presenting with discrete gray or black spots over newly formed epithelia. Risk factors of PCA in patients with TEN include host factors, iatrogenic factors, indoor environment, and wound care. Two of the four cases eventually died, highlighting the importance of further exploring PCA in patients with TEN. [ABSTRACT FROM AUTHOR]

Importance: Chronic rhinosinusitis (CRS) significantly impacts patients' quality of life and incurs substantial healthcare costs. Understanding pathogen trends before, during, and after the COVID-19 pandemic can inform better management and treatment strategies. Objective: To identify the common pathogens associated with CRS and compare them across pre-pandemic, during-pandemic, and post-pandemic periods. Design: Retrospective chart review. Setting: McGill University Health Centre, Montreal, Canada. Participants: Around 147 patients were 18 years and older, diagnosed with CRS, underwent endoscopic sinus surgery within the specified timeframe (January 2017 to September 2023), and whose charts contained relevant microbiology information. Patients were categorized into 3 groups based on surgery dates: pre- (January 2018 to November 2019), during- (January 2020 to December 2021), and post-pandemic (February 2022 to September 2023). Main Outcome Measures: Distribution and prevalence of pathogens associated with CRS across the 3 time periods. Microbiology results from nasal cultures were analyzed to identify predominant pathogens. Results: Among the 147 patients, 46 distinct organisms were identified. Staphylococcus aureus was the most prevalent pathogen, increasing during the COVID-19 period (24.7%) compared to pre-pandemic (17.9%) and post-pandemic (21.5%) periods. Significant increases during the COVID-19 period were noted for Aspergillus fumigatus (6.8%, P <.001), Enterobacter cloacae (6.8%, P =.01), and Cutibacterium acnes (6.8%, P =.03). Post-pandemic, significant rises were observed in Serratia marcescens (P <.001) and Achromobacter denitrificans (P =.03). Conclusions and Relevance: Significant shifts in CRS-associated pathogens occurred during the COVID-19 pandemic. Notable changes in the prevalence of S. aureus, A. fumigatus, E. cloacae, and C. acnes were observed during the pandemic, with increases in S. marcescens and A. denitrificans post-pandemic. These findings suggest that the pandemic's impact on healthcare practices and environmental factors influenced the microbial etiologies of CRS. Future research may explore the mechanisms driving these changes and their long-term implications for CRS management. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated the requirement of four enzymes including a cupin-domain containing protein for the formation of alkyl salicylaldehydes and derivatives. Heterologous expression of three biosynthetic genes from Aspergillus ustus resulted in the formation of such compounds in high-yields without involvement of a cupin analogue. [ABSTRACT FROM AUTHOR]

Background Early diagnosis of invasive fungal disease is essential for optimizing management. Although the clinical utility of fungal polymerase chain reaction (PCR) testing on plasma and bronchoalveolar lavage (BAL) has been established, the role of follow-up testing remains unclear. Methods This was a retrospective single-center study. The yield of follow-up PCR for Aspergillus species, Mucorales agents, Fusarium species, Scedosporium species, dimorphic fungi, Pneumocystis jirovecii , and Candida species on plasma and/or BAL was measured at intervals of 1, 2, 3, and 4 weeks following a negative result. Results A total of 1389 follow-up tests on 406 plasma specimens from 264 patients and 983 BAL specimens from 431 patients were evaluated. Overall, the positivity rate at 1, 2, 3, and 4 weeks was 2.7% (4/148), 3.3% (4/123), 5.1% (4/78), and 3.5% (2/57), respectively, on plasma, and 0% (0/333), 0.3% (1/288), 0.4% (1/228), and 0.7% (1/134), respectively, on BAL. Conversions occurred with Aspergillus species, Mucorales agents, and Fusarium species PCR on plasma and Aspergillus species and P jirovecii PCR on BAL. All patients who converted were immunocompromised. Within 1 week of a prior negative test, 2 Aspergillus and 2 Mucorales PCRs were positive on plasma, and zero tests were positive on BAL. In week 1, only 1 Aspergillus species that was positive on day 7 was classified as probable fungal disease. Conclusions Fungal PCR follow-up testing on plasma and BAL within 4 weeks of a prior negative result was of low yield and rarely generated a positive result considered clinically significant in the first week. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Development of brain abscess following solid organ transplantation is associated with significant morbidity and mortality. We undertook a descriptive study to evaluate the etiology, clinical manifestations, diagnosis, management, and outcomes of brain abscess in solid organ transplant (SOT) recipients at three major transplant centers in the United States.This is a retrospective study of adults with brain abscess following SOT between January 2000 and June 2021 at Mayo Clinic sites in Arizona, Minnesota, and Florida.A total of 39 patients were diagnosed with a brain abscess following SOT. The most common pathogens were Nocardia sp. (24 cases, 61.5% [Nocardia farcinica, 37.5%]), followed by fungi (12 cases, 30.7% [Aspergillus sp., 83.3%]). The majority were kidney transplant recipients (59%). Median time to brain abscess diagnosis was 1.3 years (range, 29 days–12 years) after SOT; 10 of 12 patients (83%) with fungal brain abscess were diagnosed within 1 year after SOT. Twelve patients underwent brain biopsy for diagnosis (25% Nocardia vs. 50% fungal), eight (20.5%) underwent surgical resection of the abscess, and 31 (79.5%) received antimicrobial therapy alone. Median time to brain abscess resolution was 166 days for Nocardia and 356 days for fungal pathogens. Eleven of 39 patients (28.2%) died as a result of their brain abscess, including four of 24 patients (16%) with Nocardia and six of 10 patients (60%) with Aspergillus brain abscess. All‐cause mortality was 43.6%.Brain abscess remains an uncommon infectious complication following SOT. Nocardia and fungi accounted for 92% of pathogens in our cohort. Fungal brain abscess portends a poor prognosis. [ABSTRACT FROM AUTHOR]

This study aimed to examine fungi diversity in dried beef meat sold in Ekiti State, characterize the isolated fungi, and determine the aflatoxin-producing ability of the Aspergillus fungi in the samples. Dried beef meat was collected from different markets in Ekiti State and screened for the presence of filamentous fungi using molecular methods. Samples were cultured aseptically on potato dextrose agar (PDA) for fungi isolation, and molecular identification was performed using DNA extraction, Polymerase chain Reaction (PCR), ITS-1/ITS-4 primer pair, and nucleotide sequencing. The results obtained indicated a range of filamentous fungi genera including Aspergillus, Rhizopus, Penicillium, Fusarium, Cladosporium, Alternaria, and other fungi species contaminating the dried meat at (43%), (42%), (3%), (2%), (2%), (1%), and (7%), respectively. High incidences were recorded for Aspergillus flavus, Aspergillus niger, and Aspergillus fumigatus in most of the screened samples. Aspergillus flavus accounted for (24.7%) of all the Aspergillus species isolated with the presence of the gene needed for aflatoxin production. The occurrences of these filamentous fungal species pose a cause for concern, as most of these fungal species are known producers of certain toxic substances. Maximum likelihood phylogenetic analysis showed a high similarity index score, which indicated a good relationship between isolated Aspergillus Species and the closely related strains from GenBank, isolated from different sources and countries. The implication of this study is that consumer health may be at risk through exposure to contaminated dried meat. [ABSTRACT FROM AUTHOR]

Genes flbA-E are involved in sporulation and vegetative growth in Aspergillus nidulans. Inactivation of either of these genes results in a fluffy phenotype with delayed or even abolished sporulation. Previously, a non-sporulating phenotype was obtained by inactivating flbA in Aspergillus niger, which was accompanied by lysis, thinner cell walls, and an increased secretome complexity. Here, we further studied the role of the flb genes of A. niger. Strains ΔflbA, ΔflbB and ΔflbE showed increased biomass formation, while inactivation of flbA-D reduced, or even abolished, formation of conidia. Strain ΔflbA was more sensitive to H2O2, DTT, and the cell wall integrity stress compounds SDS and Congo Red (CR). Also, ΔflbC was more sensitive to SDS, while ΔflbB, ΔflbD, and ΔflbE were more sensitive to CR. On the other hand, inactivation of flbE increased resistance to H2O2. Enzyme secretion was impacted when the Δflb strains were grown on xylose. Strain ΔflbE showed reduced xylanase, cellulase and amylase secretion. On the other hand, amylase secretion at the periphery of the ΔflbA colony was reduced but not in its center, while secretion of this enzyme was increased in the center of the ΔflbB colony but not at its periphery. Inactivation of flbC and flbD also impacted zonal cellulase and amylase activity. Together, the Flb protein family of A. niger function in biomass formation, sporulation, stress response, and protein secretion. [ABSTRACT FROM AUTHOR]

Indoleamine 2,3‐dioxygenase (IDO) is a monomeric heme enzyme that catalyzes the oxidative cleavage of tryptophan (L‐Trp) to form N‐formyl‐kynurenine. Similar to other heme proteins, IDO only binds to O2 when the heme iron is ferrous (FeII), thereby rendering the enzyme active. Thus, ascorbate (Asc, a reducing agent) and methylene blue (MB, an electron carrier) are commonly added to in vitro IDO assay systems. However, Asc and MB have been recently reported to significantly impact the measurement of the enzymatic parameters of vertebrate IDO. Aspergillus fumigatus is a filamentous fungus and the most common cause of invasive aspergillosis; it has three IDO genes (IDOα, IDOβ, and IDOγ). The FeII–O2 IDOs of A. fumigatus, particularly FeII–O2 IDOγ, have relatively long half‐lives in their autoxidation; however, the autoxidation was accelerated by Asc. Similar to vertebrate IDOs, Asc acted as a competitive (or mixed‐competitive) inhibitor of the IDOs of A. fumigatus. A positive correlation (in the order of IDOγ > IDOβ > IDOα) was observed between the inhibitory sensitivity of the IDOs to Asc and the facilitation of their autoxidation by Asc. The FeII–O2 IDO can repeat the dioxygenase reaction as long as it reacts with L‐Trp; however, substrate‐free FeII–O2 IDO is converted into inactive FeIII–IDO by autoxidation. Thus, L‐Trp (which keeps the IDO active) competes with Asc (which inactivates IDO by accelerating autoxidation). This is probably why Asc, which is structurally quite different from L‐Trp, appears to function as a competitive (or mixed‐competitive) inhibitor of IDOs. [ABSTRACT FROM AUTHOR]

NKG2D is a central activating receptor involved in target recognition and killing by Natural Killer and CD8+ T cells. The known role of NKG2D is to recognize a family of self-induced stress ligands that are upregulated on stressed cells such as cancerous or virally infected cells. Fungal pathogens are a major threat to human health, infecting more than a billion patients yearly and becoming more common and drug resistant. Here we show that NKG2D plays a critical role in the immune response against fungal infections. NKG2D can recognize fungal pathogens from most major families including Candida, Cryptococcus and Aspergillus species, and mice lacking NKG2D are extremely sensitive to fungal infections in models of both invasive and mucosal infections, making NKG2D an anti-fungal pattern recognition receptor. NKG2D is a central activating receptor know to recognise stress ligangs upregulated during cancer or infection. Here, Charpak-Amikam et al show that NKG2D also recognises fungal pathogens and plays a critical role in mounting an appropriate immune response to them. [ABSTRACT FROM AUTHOR]

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic lung disorder characterized by an exaggerated immune response to fungal allergens, particularly from Aspergillus fumigatus. ABPA leads to excessive mucus production and impaired mucociliary clearance. When A. fumigatus conidia are inhaled, they germinate, release exoproteases and other substances that further impede mucociliary clearance, and activate the immune response. The immune response is known by an exaggerated Th2 response to Aspergillus antigens, leading to production of IgE antibodies, eosinophilic infiltration of the lungs, and the formation of immune complexes. These immune complexes can deposit in the lung tissue, leading to airway inflammation, bronchiectasis, and fibrosis. This disease mainly occurs in individuals diagnosed with bronchial asthma and cystic fibrosis. Increased levels of A. fumigatus total IgE and specific IgE, IgG, and IgA antibodies, play a role in diagnosing patients with ABPA. [ABSTRACT FROM AUTHOR]

Concurrent tuberculosis and fungal otitis media complicated with skull base osteomyelitis is a rare and intricate clinical entity, particularly in well-controlled diabetes mellitus patients with unusual symptomatology. We present the case of an elderly gentleman with well-controlled type II diabetes mellitus who endured four months of chronic left ear pain, left-sided temporal headaches, and left ear pulsatile tinnitus, which persisted despite multiple courses of antibiotics. Initial investigations yielded conflicting suggestions, indicating the possibility of either an infection or the presence of a glomus tumor. However, intraoperative samples sent for microbiological and histological investigation revealed the presence of Aspergillus Niger and Mycobacterium complex. Treatment with antifungal and antituberculosis agents led to a remarkable improvement in the patient's clinical symptoms and radiological and biochemical markers. [ABSTRACT FROM AUTHOR]

Objectives: Allergic bronchopulmonary aspergillosis (ABPA) is a complex lung disease associated with significant morbidity. The ABPA Working Group (AWG) of the International Society for Human and Animal Mycology (ISHAM) revised their management guidelines in 2024, but there is currently no standardised tool to assess adherence to these recommendations. Methods: We extracted key recommendations from the updated 2024 ISHAM‐AWG guidelines, focusing on critical areas: screening and diagnosis of ABPA, managing acute and treatment‐dependent ABPA, and monitoring treatment response. Each item was assigned a score ranging from zero to three. We assigned negative scores to interventions not recommended by the guidelines. Results: We identified 38 items indicative of optimal clinical care for patients with ABPA. The score for screening asthmatics for ABPA was set at three points. For diagnosing ABPA, 16 items were included, with a score ranging from 12 to 16 points, depending on the specific components used (predisposing conditions, serum A. fumigatus‐specific IgE and IgG, serum total IgE, blood eosinophil count and chest computed tomography). The management of acute ABPA comprised 11 items, with a maximum score of three points. For treatment‐dependent ABPA, there were nine items (scores ranging from −3 to 6). Follow‐up care comprised 10 items with a maximum score of 10–13 points, covering imaging, spirometry, testing serum total IgE levels and therapeutic drug monitoring. Conclusions: The EQUAL ABPA score has been developed as a comprehensive tool to quantify guideline adherence. Future studies will evaluate to which extent guideline adherence is associated with improved clinical outcomes for patients with ABPA. [ABSTRACT FROM AUTHOR]

Objectives: Chronic pulmonary aspergillosis (CPA) is a fungal lung infection characterised by the slowly progressing destruction of the lung parenchyma and has four main subtypes. The objective of this work was to evaluate the epidemiology of CPA in our area and evaluate the involvement of the different subtypes in mortality. Methods: This was a descriptive longitudinal retrospective study developed in three tertiary hospitals in Spain. Among all patients admitted with a pulmonary aspergillosis diagnosis, we selected those who fulfilled the criteria for chronic aspergillosis according to the criteria of Denning, excluding those with a haematological disorder. Results: Among 409 inpatients recorded as having a pulmonary aspergillosis infection, only 76 (18.5%) fulfilled the criteria for CPA, with an estimated incidence of 0.67 cases/100,000 inhabitants/year. The subtypes detected were subacute invasive aspergillosis (SAIA) in 33 (43.4%) patients, simple aspergilloma (SA) in 25 (32.9%) patients, cavitary chronic aspergillosis (CCPA) in 13 (17.1%) patients, and chronic fibrosis (CFPA) in five (6.5%) patients. The overall three-month mortality rate was 23%, which was higher in SAIA patients. The predictors of early mortality were age > 65 years (OR 3.0 CI 95 1.0–9.5 p = 0.043) and the SAIA subtype vs. other subtypes (OR 3.1 CI 95 1.0–9.5 p = 0.042). Conclusions: The incidence rate estimated was inferior to that previously reported. The three-month mortality in patients with CPA was high, with older age and the SAIA subtype being the variable independent predictors of a worse prognosis. [ABSTRACT FROM AUTHOR]

Mycotoxin contamination of food and feed is a worldwide problem that needs to be addressed with highly efficient and biologically safe techniques. RNA interference (RNAi) is a natural mechanism playing an important role in different processes in eukaryotes, including the regulation of gene expression, maintenance of genome stability, protection against viruses and others. Recently, RNAi-based techniques have been widely applied for the purposes of food safety and management of plant diseases, including those caused by mycotoxin-producing fungi. In this review, we summarize the current state-of-the-art RNAi-based approaches for reducing the aggressiveness of key toxigenic fungal pathogens and mycotoxin contamination of grain and its products. The ways of improving RNAi efficiency for plant protection and future perspectives of this technique, including progress in methods of double-stranded RNA production and its delivery to the target cells, are also discussed. [ABSTRACT FROM AUTHOR]

Fungal growth on cellulose-based materials in libraries can have detrimental effects on books and documents. This biodeterioration affects their physical, chemical, and esthetical characteristics. Thus, this work aimed to assess fungal aerosols' concentrations and biodeterioration risk in two public libraries with artificial ventilation: the Banco de la República and CAJAMAG libraries. Air sampling was performed using a two-stage viable Andersen cascade impactor with Sabouraud dextrose agar at 4% on Petri dishes. Also, the temperature and relative humidity were measured with a digital thermo-hygrometer HOBO U12 Data Logger. The concentrations were low, with values of around 35 CFU/m3. Aspergillus, Cladosporium, and Penicillium were the predominant genera in the two libraries, with A. niger being the most abundant species. The thermo-hygrometric conditions inside the libraries were stable, with a mean temperature of 25.2 °C and a mean relative humidity of 52.1%. The calculated potential risk associated with fungal aerosols was seen to be medium in both libraries, where Aspergillus genera reported the highest cellulosic activity and hence had a higher risk of biodeterioration. [ABSTRACT FROM AUTHOR]

Simple Summary: The domesticated carmine cochineal produces pigments used in food, cosmetics, and the textile industry. Its use dates to the pre-Hispanic period and thus is an Amerindian legacy. Cochineals grow and feed on the edible leaves of cacti. Since insects feed on plant sap, they may obtain their microbes from the plants and indeed we found here that some of the fungi in the insect guts are the same as those encountered in cacti. Fungi may help in digestion as they are capable of breaking down plant polymers in cultures and inside guts. We found fungi inside cochineals during microscopic examinations using different procedures to detect fungi. One of the isolated fungi produces a purple pigment that resembles the carminic acid. This study identified several potential functions of cochineal fungi and examined their plant origin. The cochineal insect Dactylopius coccus Costa (Hemiptera) has cultural and economic value because it produces carminic acid that is used commercially. In this study, distinct fungi were cultured from dissected tissue and identified as Penicillium, Coniochaeta, Arthrinium, Cladosporium, Microascus, Aspergillus, and Periconia. Fungi were microscopically observed inside cochineals in the gut, fat body, and ovaries. Since cochineals spend their lives attached to cactus leaves and use the sap as feed, they can obtain fungi from cacti plants. Indeed, we obtained Penicillium, Aspergillus, and Cladosporium fungi from cacti that were identical to those inside cochineals, supporting their plant origin. Fungi could be responsible for the degrading activities in the insect guts, since cellulase, pectinase, and amylase enzymatic activities in insect guts decreased in fungicide-treated cochineals. Our findings set the basis for the further study of the interactions between insects, fungi, and their host plants. [ABSTRACT FROM AUTHOR]

Objectives: To study the predisposing factors, treatment, and complications of Aspergillus otitis externa. Methods: A retrospective analysis of patients diagnosed with Aspergillus otitis externa at the Department of Otorhinolaryngology, Helsinki University Hospital, between January 2010 and December 2018 was performed. Results: Of the 269 Aspergillus otitis externa (OE) patients, 96 developed otitis media (OM) and 7 developed mastoiditis. Antibiotic and steroid treatment and otological history were risk factors for Aspergillus OE. Systemic diseases and immunocompromising states were more common in mastoiditis patients. Repetitive ear cleaning and topical drugs are primary treatments, but systemic drugs and surgery were needed in resistant and invasive cases. Forty‐five novel tympanic membrane (TM) perforations were reported. A strong association between Aspergillus species and final infection types was found; A. niger was the dominant species in OM and in novel TM perforations, whereas A. flavus and A. fumigatus caused mastoiditis. Some of the TM perforations persisted despite treatment. Permanent hearing impairment was associated with OM and mastoiditis. Conclusion: As Aspergillus OE has the potential to cause acute and chronic complications, fungal OE should be suspected early on if the infection persists after conventional treatment. The identification of Aspergillus species could aid in spotting patients at risk for more severe disease and complications. Intensive local treatment is sufficient in most cases of OE and OM but effective topical antifungals are limited. Patients with Aspergillus OM and mastoiditis should be followed up for hearing impairment and permanent TM perforations after the infection resolves. Level of evidence: Level 4 (The Oxford 2011 Levels of Evidence). Aspergillus otitis externa may lead to a wide range of frequent and rare complications, including tympanic membrane perforations, otitis media, mastoiditis, permanent hearing loss, and cranial nerve palsies. Aspergillus niger causes most otitis media and tympanic membrane perforations, whereas A. flavus, A. fumigatus, and immunocompromising states are predispoding factors for mastoiditis. Careful local treatment is efficient in most cases but surgery and systemic antifungals are needed in profound infections. [ABSTRACT FROM AUTHOR]

Grapevines constitute a very important crop in Greece and ochratoxin A (OTA) contamination of grapes is one of the most serious problems. The main aim of this study was to investigate the fungicidal activity of the fungicide Switch 62.5WG (37.5% v/v cyprodinil + 25% v/v fludioxonil) and Rhapynal (80% rhamnolipids) to reduce the black Aspergillus spp. (section Nigri) population and OTA contamination of grapes grown in Greece. Applications with the above products were conducted both at the harvesting stage and after cold storage. The results showed that pre-harvest applications with Switch 62.5WG or Switch 62.5WG + Rhapynal generally reduced the black Aspergillus spp. population, but not the OTA contamination of grapes. However, a repeated application after cold storage further reduced the black Aspergillus spp. population and significantly reduced the OTA contamination of grapes. Generally, this study showed that it is possible to reduce the black Aspergillus spp. population, but not the ochratoxin A contamination of grapes by spray applications with the fungicide Switch 62.5WG. However, fungicide application to grapes immediately after cold storage (2 months) could reduce ochratoxin A contamination of grapes and further reduce the black Aspergillus spp. population. [ABSTRACT FROM AUTHOR]

Background New antifungal agents are required to mitigate against azole-resistant Aspergillus and drug-resistant non- Aspergillus moulds. The novel orotomide, olorofim (F2G, Manchester, UK), has potent fungicidal activity against Aspergillus including azole-resistant Aspergillus fumigatus, Lomentospora prolificans and Scedosporium spp. Development of olorofim-specific clinical breakpoints/epidemiological cut-off values requires reliable MIC data. Objectives Determine the in vitro activity of olorofim compared with standard antifungals against mould pathogens at an Australian hospital. Materials and methods Olorofim MICs were determined for 507 clinical mould isolates using the CLSI M38-A3 standard. MICs of amphotericin B, anidulafungin, posaconazole, voriconazole and isavuconazole were obtained using Sensititre™ YeastOne YO10 and AUSNMRCI panels (Thermo-Fisher Scientific). Results A. fumigatus sensu stricto was the commonest species (33.3%) followed by L. prolificans (18.3%), Scedosporium (11.4%) and Fusarium (6%) species. Olorofim modal MICs were ≤0.25 mg/L (MIC90 0.25 mg/L) for all Aspergillus except Aspergillus Section Usti (1 mg/L); MICs for nine azole-resistant/non-wild-type A. fumigatus ranged from 0.008 to 0.125 mg/L. The MIC90 of olorofim for L. prolificans was 0.5 mg/L, 0.25–0.5 mg/L for Scedosporium spp. and 8 mg/L for the F. solani complex but with modal MICs of 0.25 and 0.008 mg/L for F. oxysporum and F. proliferatum complexes, respectively. For Verruconis gallopava (n  = 10), the olorofim MIC90 was 0.06 mg/L (voriconazole MIC90 2 mg/L, isavuconazole MICs of 4–>8 mg/L). Olorofim had little activity against other dematiaceous moulds including Exophiala species. Conclusions Olorofim was highly active against Aspergillus spp. including azole-resistant A. fumigatus , L. prolificans , Scedosporium spp. and some Fusarium species with the new finding of potent activity against V. gallopava. [ABSTRACT FROM AUTHOR]

Methanol reportedly stimulates citric acid (CA) production by Aspergillus niger and A. tubingensis ; however, the underlying mechanisms remain unclear. Here, we elucidated the molecular functions of the citrate exporter gene cexA in relation to CA production by A. tubingensis WU-2223L. Methanol addition to the medium containing glucose as a carbon source markedly increased CA production by strain WU-2223L by 3.38-fold, resulting in a maximum yield of 65.5 g/L, with enhanced cexA expression. Conversely, the cexA -complementing strain with the constitutive expression promoter Ptef1 (strain LhC-1) produced 68.3 or 66.7 g/L of CA when cultivated without or with methanol, respectively. Additionally, strain LhC-2 harboring two copies of the cexA expression cassette produced 80.7 g/L of CA without methanol addition. Overall, we showed that cexA is a target gene for methanol in CA hyperproduction by A. tubingensis WU-2223L. Based on these findings, methanol-independent CA-hyperproducing strains, LhC-1 and LhC-2, were successfully generated. [ABSTRACT FROM AUTHOR]

Otomycosis is a chronic or subacute fungal infection of external ear accounting to 5 to 20% of external ear infection worldwide. Literature has suggested multiple local and environmental host factors associated with otomycosis, but their strength of association is not well established. We did this review to analyse otomycosis with respect to it's various common predisposing factors. Human studies reporting ototopical antibiotics with or without steroids as predisposing factors for otomycosis, or pooled data together with other predisposing factors were included. MEDLINE, EMBASE, CINAHL, the ISRCTN register, and Cochrane databases were searched for the data extraction. Critical appraisal was done using the standardized Joanna Briggs Institute's (JBI) Appraisal checklist. Random effects were used to calculate pooled estimate prevalence with 95% Confidence Intervals (CIs). Age varied in different studies with a mean age variation from 7 to 43.19. Most of the studies were conducted in tropical and sub-tropical countries. Aspergillus was the most common species isolated. The use of ototopical antibiotics with or without steroid drops [47% (95% CI, 0.38 - 0.56)] were found to be the commonest predisposing factor for otomycosis, followed by the use of a variety of oils and wax solvents [38% (95% CI,0.26 - 0.51)] and trauma to the External Auditory Canal (EAC) as a result of compulsive cleaning or instrumentation[37% (95% CI, 0.21 - 0.54)]. We suggest the need for caution and vigilance from clinicians treating patients with ototopical drops for ear infections and use of other alternative treatment like 2% acetic acid for mild cases whenever feasible. [ABSTRACT FROM AUTHOR]

Background: The utility of two disease-severity indices, namely bronchiectasis severity index (BSI) and FACED score in allergic bronchopulmonary aspergillosis (ABPA) remains unknown. Objective: To correlate the BSI and FACED scores with immunological parameters (serum IgE [total and A. fumigatus-specific], A. fumigatus-specific IgG, blood eosinophil count), and high-attenuation mucus on chest computed tomography in ABPA. The secondary objectives were to evaluate the correlation between BSI and FACED scores and correlate the BSI/FACED scores with the bronchiectasis health questionnaire (BHQ) and Saint George's Respiratory Questionnaire (SGRQ). Methods: We included treatment-naïve ABPA subjects with bronchiectasis in a prospective observational study. We computed the BSI and FACED scores for each subject before initiating treatment. The subjects also completed two quality-of-life questionnaires (BHQ and SGRQ). Results: We included 91 subjects. The mean (standard deviation) BSI and FACED scores were 3.43 (3.39) and 1.43 (1.27). We found no correlation between BSI or FACED with any immunological parameter or high-attenuation mucus. There was a strong correlation between BSI and FACED scores (r = 0.76, p < 0.001). We found a weak correlation between BSI and BHQ/SGRQ and FACED and SGRQ. Conclusion: We found no correlation between BSI and FACED with immunological parameters in ABPA. However, we found a significant correlation between BSI and FACED and a weak correlation between SGRQ and BHQ. ABPA likely requires a separate disease-severity scoring system. [ABSTRACT FROM AUTHOR]

The aim of this study is to develop safe biological methods for controlling fungal deterioration of historical manuscripts. Therefore, fifteen fungal isolates were obtained from paper sheets and leather skins of a deteriorated historical manuscript (dated back to the 13th century). Those isolates were identified using both traditional methods and ITS-sequencing analysis. Aspergillus niger accounted for seven strains, Penicillium citrinum for one strain, Aspergillus flavus for three, Aspergillus fumigatus for one, Aspergillus nidulans for one, and Penicillium chrysogenum for two of the fungal strains that were obtained. The ability of fungal strains for the secretion of cellulase, amylase, gelatinase, and pectinase as hydrolytic enzymes was evaluated. The capability of the probiotic-bacterial strain Lactobacillus plantarum DSM 20174 for inhibition of fungal strains that cause severe deterioration was studied using ethyl acetate-extract. The metabolic profile of the ethyl acetate-extract showed the presence of both high- and low-molecular-weight active compounds as revealed by GC-MS analysis. The safe dose to prevent fungal growth was determined by testing the ethyl acetate extract's biocompatibility against Wi38 and HFB4 as normal cell lines. The extract was found to have a concentration-dependent cytotoxic impact on Wi38 and HFB4, with IC 50 values of 416 ± 4.5 and 349.7 ± 5.9 μg mL−1, respectively. It was suggested that 100 μg mL−1 as a safe concentration could be used for paper preservation. Whatman filter paper treated with ethyl acetate extract was used to cultivate the fungal strain Penicillium citrinum AX2. According to data analysis, fungal inhibition measurement, SEM, ATR-FT-IR, XRD, color change measurement, and mechanical property assessment, the recommended concentration of ethyl acetate extract was adequate to protect paper inoculated with the highest enzymatic producer fungi, P. citrinum AX2. [Display omitted] • Several fungal strains were obtained from old historical manuscripts. • The fungal strains were identified and investigated for enzymatic activities. • Probiotic L. plantarum DSM20174 metabolites were used to biocontrol fungal growth. • Ethyl acetate extract shows biocompatibility with Wi38 and HFB4 normal cell lines. • SEM, ATR-FT-IR, XRD, and mechanical properties recommended the extract application. [ABSTRACT FROM AUTHOR]

Fructooligosaccharides are prebiotic sugars that are widely used in the production of functional foods, which can be produced enzymatically by the transfructosylation reaction of sucrose. This work aimed to optimize the production of an invertase with high transfructosylation activity from Aspergillus carbonarius PC-4 using pineapple crown as the inducer substrate and evaluate its biochemical properties. The culture medium was optimized using a Plackett–Burman experimental design and a central composite rotatable design, resulting in a maximum transfructosylation activity of 65.33 U/mL at 72 h of cultivation. The cultivation parameters were Yp/s = 1070.75 U/g and PP = 2771.48 U/h, which showed an increase of 5.2-fold in the enzyme produced. The optimum temperature (50 °C) and pH (5.0) for the enzymatic activity were obtained by a CCR design. The enzyme showed a half-life of 60 min at 40 °C. In conclusion, the invertase produced from A. carbonarius PC-4 using agro-industrial waste (pineapple crown) and an inorganic nitrogen source (ammonium nitrate) exhibits high transfructosylation activity that can be used as a potential source for the production of fructooligosaccharides. [ABSTRACT FROM AUTHOR]

Fungi of the genus Aspergillus are widespread in the environment, where they produce large quantities of airborne conidia. Inhalation of Aspergillus spp. conidia in immunocompromised individuals can cause a wide spectrum of diseases, ranging from hypersensitivity responses to lethal invasive infections. Upon deposition in the lung epithelial surface, conidia encounter and interact with complex microbial communities that constitute the lung microbiota. The lung microbiota has been suggested to influence the establishment and growth of Aspergillus spp. in the human airways. However, the mechanisms underlying this interaction have not yet been sufficiently investigated. In this study, we aimed to enrich and isolate bacterial strains capable of inhibiting the germination and growth of A. fumigatus conidia from bronchoalveolar lavage fluid (BALF) samples of lung transplant recipients using a novel enrichment method. This method is based on a soft agar overlay plate assay in which bacteria are directly in contact with conidia, allowing inhibition to be readily observed during enrichment. We isolated a total of five clonal bacterial strains with identical genotypic fingerprints, as shown by random amplified polymorphic DNA PCR (RAPD–PCR). All strains were identified as Pseudomonas aeruginosa (strains b1–b5). The strains were able to inhibit the germination and growth of Aspergillus fumigatus in a soft agar confrontation assay, as well as in a germination multiplate assay. Moreover, when compared with ten P. aeruginosa strains isolated from expectoration through standard methods, no significant differences in inhibitory potential were observed. Additionally, we showed inhibition of A. fumigatus growth on Calu-3 cell culture monolayers. However, the isolated P. aeruginosa strains were shown to cause significant damage to the cell monolayers. Overall, although P. aeruginosa is a known opportunistic lung pathogen and antagonist of A. fumigatus, we validated this novel one-step enrichment approach for the isolation of bacterial strains antagonistic to A. fumigatus from BALF samples as a proof-of-concept. This opens up a new venue for the targeted enrichment of antagonistic bacterial strains against specific fungal pathogens. [ABSTRACT FROM AUTHOR]

Aspergillus spp. are common dominant fungi in the moldy agricultural products. Different Aspergillus species exhibit high morphological and genetic sequence similarity, making identification challenging. The measurement of mycelial growth in these Aspergillus species often requires a relatively long time. Therefore, there is a need to develop a new rapid method for identifying Aspergillus species and monitoring their growth. The volatile compounds released by five Aspergillus species on culture media were detected by gas chromatography-mass spectrometer (GC–MS), electronic nose and headspace-gas chromatography-ion migration spectrometry (HS-GC-IMS), their characteristic volatile signals were captured, the models for identifying Aspergillus species were established, and prediction models for mycelial growth of five Aspergillus species were developed. The results showed that the LDA classification training set model constructed using the fusion of GC-IMS and electronic nose data achieved a 100% accuracy rate for identifying Aspergillus species in the training set and an 83.3% accuracy rate in the test set, significantly outperforming models based on HS-GC-IMS or electronic nose data alone. When the result combined with morphological analysis, a 100% accuracy rate in identifying Aspergillus species could be achieved. The partial least squares regression (PLSR) prediction models for mycelial growth in Aspergillus species, constructed using both fusion electronic nose data and HS-GC-IMS data, demonstrated high accuracy with prediction accuracies greater than 0.972 for all five species. The prediction model based solely on electronic nose data had lower accuracy, while models using HS-GC-IMS data alone or its combined with electronic nose data achieved good results. This fusion approach of HS-GC-IMS and electronic nose might have the potential to serve as a preliminary screening tool for fungi identification. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months. Methods: Prospective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4 months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation. Results: Four cases of invasive aspergillosis were diagnosed in 4 months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles. Conclusion: We have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR34/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development. [ABSTRACT FROM AUTHOR]

Background. Since the ants play a key role in transmitting microorganisms, it is important to identify the fungal species isolated from the external surfaces of ants caught from hospitals. Therefore, the present study aimed to identify the fungal species isolated from the external surfaces of ants caught from Babol hospitals. Methods. Ants were collected by trapping inside sterile tubes and were washed with normal saline for 20 seconds. Then, 100 μL of the resulting solution was cultured in Sabouraud Dextrose Agar (SDA) medium and incubated for one week at 35C°. Macroscopic, microscopic, and RFLP-PCR molecular techniques were employed to confirm the grown isolates. Results. A total of 79 fungal isolates including 47 isolates of hyaline fungi (59.49%) and 32 isolates of black fungi (40.51%) were obtained from 63 captured ants. Out of 47 cultured fungi, 15 fungi (31.91%) were Aspergillus niger and 15 (31.91%) were A. flavus, 12 (25.53%) were A. fumigatus and 5 isolates were Penicillium (10.63%). Conclusion. Taking into account the increasing number of immunocompromised patients, outbreak of COVID-19 in recent years, and numerous reports about the invasive fungal diseases among COVID-19 patients, it was found necessary to control the ants as carriers of these organisms. Practical Implications. It was necessary to control these insects effectively in order to prevent the increasing prevalence of the fungal diseases among the hospitalized people. [ABSTRACT FROM AUTHOR]

Calcineurin–nuclear factor of activated T cells (CN-NFAT) inhibitors are widely clinically used drugs for immunosuppression, but besides their required T cell response inhibition, they also undesirably affect innate immune cells. Disruption of innate immune cell function can explain the observed susceptibility of CN-NFAT inhibitor–treated patients to opportunistic fungal infections. Neutrophils play an essential role in innate immunity as a defense against pathogens; however, the effect of CN-NFAT inhibitors on neutrophil function was poorly described. Thus, we tested the response of human neutrophils to opportunistic fungal pathogens, namely Candida albicans and Aspergillus fumigatus , in the presence of CN-NFAT inhibitors. Here, we report that the NFAT pathway members were expressed in neutrophils and mediated part of the neutrophil response to pathogens. Upon pathogen exposure, neutrophils underwent profound transcriptomic changes with subsequent production of effector molecules. Importantly, genes and proteins involved in the regulation of the immune response and chemotaxis, including the chemokines CCL2 , CCL3 , and CCL4 were significantly upregulated. The presence of CN-NFAT inhibitors attenuated the expression of these chemokines and impaired the ability of neutrophils to chemoattract other immune cells. Our results amend knowledge about the impact of CN-NFAT inhibition in human neutrophils. [ABSTRACT FROM AUTHOR]

Fungal infections pose an increasing threat to public health. New pathogens and changing epidemiology are a pronounced risk for nosocomial outbreaks. To investigate clonal transmission between patients and trace the source, genotyping is required. In the last decades, various typing assays have been developed and applied to different medically important fungal species. While these different typing methods will be briefly discussed, this review will focus on the development and application of short tandem repeat (STR) genotyping. This method relies on the amplification and comparison of highly variable STR markers between isolates. For most common fungal pathogens, STR schemes were developed and compared to other methods, like multilocus sequence typing (MLST), amplified fragment length polymorphism (AFLP) and whole genome sequencing (WGS) single nucleotide polymorphism (SNP) analysis. The pros and cons of STR typing as compared to the other methods are discussed, as well as the requirements for the development of a solid STR typing assay. The resolution of STR typing, in general, is higher than MLST and AFLP, with WGS SNP analysis being the gold standard when it comes to resolution. Although most modern laboratories are capable to perform STR typing, little progress has been made to standardize typing schemes. Allelic ladders, as developed for Aspergillus fumigatus, facilitate the comparison of STR results between laboratories and develop global typing databases. Overall, STR genotyping is an extremely powerful tool, often complimentary to whole genome sequencing. Crucial details for STR assay development, its applications and merit are discussed in this review. [ABSTRACT FROM AUTHOR]

Background: Clinical amyopathic dermatomyositis is characterized by cutaneous symptoms but lacks muscle symptoms. Anti-melanoma differentiation-associated gene 5 antibodies are frequently found in Japanese patients with clinical amyopathic dermatomyositis. Patients with rapidly progressive interstitial lung disease with positive anti-melanoma differentiation-associated gene 5 antibodies have poor prognoses, and majority of them are treated with combination immunosuppressive therapy; however, the best treatment is yet to be determined. Case presentation: A 52-year-old Asian male patient presented with a chief complaint of dyspnea on exertion. He had a typical skin rash and rapidly progressive interstitial pneumonia. Additionally, anti-melanoma differentiation-associated gene 5 antibodies were detected; therefore, he was diagnosed with dermatomyositis-associated interstitial pneumonia. Respiratory failure worsened despite administering steroid pulse therapy, tacrolimus, and cyclophosphamide. Consequently, plasma exchange was performed on day 13 of admission. After a slight improvement, the patient's respiratory failure worsened. Thus, cyclophosphamide was replaced by tofacitinib on day 28. Although respiratory failure improved and the progression of interstitial pneumonia seemed under control, βD-glucan level increased and Aspergillus antigen was detected on day 49. Micafungin and voriconazole were administered, but the patient succumbed to worsening respiratory failure on day 61. The pathological autopsy revealed multiple nodular lesions with cavity formation in both lungs and the presence of Aspergillus with severe neutrophilic infiltration and necrosis, which supported the diagnosis of invasive pulmonary aspergillosis. Conclusion: The patient with anti-melanoma differentiation-associated gene 5 antibody-related rapidly progressive interstitial lung disease, whose disease was difficult to control after the administration of triple immunosuppressive therapy (steroids, tacrolimus, and cyclophosphamide), showed good response with tofacitinib. Unfortunately, the patient died of invasive pulmonary aspergillosis owing to severe immunosuppression; thus, the signs of complications should be promptly detected. [ABSTRACT FROM AUTHOR]

Antifungal resistance remains a significant public health threat, yet poorly investigated. This study for the first time investigated the antifungal profile of moulds isolated from groundwaters in a rural community of Osun State, Southwest Nigeria. Groundwater samples were collected during dry and rainy seasons, and processed for mould isolation using standard methods. The isolates were presumptively identified and screened for in vitro susceptibility using 4 antifungals conventionally employed in clinical cases. Multiple antifungal resistance phenotypes and indices were equally evaluated. Representative of each putatively identified species were confirmed using molecular techniques. A total of 29 and 27 moulds were obtained during the dry and rainy seasons, respectively. Genus Aspergillus was the most prevalent (30.4%). Of the 56 isolates subjected to antifungal susceptibility testing, 55(98%) were resistant to fluconazole, followed by flucytosine 49(88%), ketoconazole 45(80%) and amphotericin B 31(55%). Exactly 46 isolates were multidrug-resistant, 23(50%) each, to 3 and 4 drugs, respectively. The multiple antifungal resistance index (MARI) evaluated was 1 in all the samples A-Q, except C (0.75), transcending the threshold limit of 0.2, indicating the isolates to be of high antifungal usage origin. The molecularly identified species had 99–100% similarity with reference strains from GenBank and evolutionary relationship of taxa revealed 10 distinct clades. The outcome of this study reveals a rise in the frequency of antifungal resistance in moulds towards standard drugs, thus, advocating for adequate investigations targeted at monitoring antifungal resistance in groundwater milieus. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Invasive aspergillosis (IA) can lead to life‐threatening respiratory failure necessitating extracorporeal membrane oxygenation (ECMO) support. However, data on ECMO experience in the management of IA patients are scarce.The purpose of this systematic review was to evaluate the potential benefits and risks of ECMO as a supportive intervention for critically ill patients with IA.We conducted a systematic review of the literature using the search terms ECMO, extracorporeal membrane oxygenation, Aspergillus and Aspergillosis in two databases (Medline and Scopus). Clinical data were extracted by two independent investigators. Clinical parameters, such as mode of ECMO support, duration of treatment and clinical outcomes, were assessed.Overall, 32 patients were included in the analysis. The age ranged from 5 to 69 years, 59% were male, and 38% were female. The majority of patients suffered from ARDS (82%). 82% received VV‐ECMO, and 18% received VA‐ECMO. Aspergillus fumigatus was the most frequent cause of IA, coinfections were frequently observed (51%). The overall mortality was 78%. Complications during ECMO support were observed in 21 of the 39 cases (53.8%).IA poses significant management challenges for critically ill ICU patients, even with ECMO support. Although ECMO appears to improve survival of patients at high risk of AI, potential risks such as bacterial superinfection and altered pharmacokinetics of antifungal drugs must be carefully considered. [ABSTRACT FROM AUTHOR]

Aspergillus vadensis CBS 113365, a close relative of A. niger , has been suggested as a more favourable alternative for recombinant protein production as it does not acidify the culture medium and produces very low levels of extracellular proteases. The aim of this study was to investigate the underlying cause of the non-amylolytic and non-proteolytic phenotype of A. vadensis CBS 113365. Our results demonstrate that the non-functionality of the amylolytic transcription factor AmyR in A. vadensis CBS 113365 is primarily attributed to the lack of functionality of its gene's promoter sequence. In contrast, a different mechanism is likely causing the lack of PrtT activity, which is the main transcriptional regulator of protease production. The findings presented here not only expand our understanding of the genetic basis behind the distinct characteristics of A. vadensis CBS 113365, but also underscore its potential as a favourable alternative for recombinant protein production. • Restoration of amylolytic activity of A. vadensis by introduction of A. niger amyR. • Promoter non-functionality of amyR causes low amylase activities in A. vadensis. • The prtT promoter has non-functional significance in A. vadensis. [ABSTRACT FROM AUTHOR]

Urban dumpsites are excellent sources of microbes which can biodegrade numerous materials present in waste. This study focused on the assessment of the mycodegradation potential of LDPE (Low-Density Polyethylene) by ascomycetous microfungi from urban dumpsites in Sri Lanka. Out of the collection obtained from five localities in Sri Lanka, eight species of ascomycetes, viz. Talaromyces purpureogenus (GF85), T. beijingensis (GGF03), Penicillium citrinum (GF89), Purpureocillium lilacinum (GF99), Aspergillus flavus (GF94), Aspergillus sp. (GF82), A. terreus (MMF08), and Fusarium falciforme (GF77), demonstrated mycodegradation potential based on the primary screening. All the isolates were accurately identified based on morphology, Sanger sequencing, and phylogenetic analysis of nuclear internal transcribed spacer region with 5.8 s ribosomal DNA (ITS). Among the isolates, T. purpureogenus GF85 showed a 13–17% weight reduction of LDPE. The same fungus showed evidence of remarkable ability to cause biodeterioration of LDPE by Fourier-transform infrared spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). This study highlights the significance of extensive sampling, morphological, molecular characterisation, and comparative analysis of fungi from unexplored habitats towards developing sustainable solutions for the polyethylene waste crisis. [ABSTRACT FROM AUTHOR]

Inflammation serves as an intricate defense mechanism for tissue repair. However, overactivation of TLR4-mediated inflammation by lipopolysaccharide (LPS) can lead to detrimental outcomes such as sepsis, acute lung injury, and chronic inflammation, often associated with cancer and autoimmune diseases. This study delves into the anti-inflammatory properties of "Aspergillus unguis isolate SP51-EGY" on LPS-stimulated RAW 264.7 macrophages. Through real-time qPCR, we assessed the expression levels of pivotal inflammatory genes, including iNOS, COX-2, TNF-α, and IL-6. Remarkably, our fungal extracts significantly diminished NO production and showed noteworthy reductions in the mRNA expression levels of the aforementioned genes. Furthermore, while Nrf2 is typically associated with modulating inflammatory responses, our findings indicate that the anti-inflammatory effects of our extracts are not Nrf2-dependent. Moreover, the chemical diversity of the potent extract (B Sh F) was elucidated using Q-TOF LC-HRMS, identifying 54 compounds, some of which played vital roles in suppressing inflammation. Most notably, compounds like granisetron, fenofibrate, and umbelliprenin were found to downregulate TNF-α, IL-1β, and IL-6 through the NF-κB signaling pathway. In conclusion, "Aspergillus unguis isolate SP51-EGY", isolated from the Red Sea, Egypt, has been unveiled as a promising TLR4 inhibitor with significant anti-inflammatory potentials, presenting novel insights for their potential therapeutic use in inflammation. [ABSTRACT FROM AUTHOR]

Genetic code expansion technology allows the incorporation of unnatural amino acids (UAAs) into proteins, which is useful in protein engineering, synthetic biology, and gene therapy. Despite its potential applications in various species, filamentous fungi remain unexplored. This study aims to address this gap by developing these techniques in Aspergillus nidulans. We introduced an amber stop codon into a specific sequence within the reporter gene expressed in A. nidulans and replaced the anticodon of the fungal tRNATyr with CUA. This resulted in the synthesis of the target protein, confirming the occurrence of amber suppression in the fungus. When exogenous E. coli tRNATyr CUA (Ec. tRNATyr CUA) and E. coli tyrosyl-tRNA (Ec.TyrRS) were introduced into A. nidulans , they successfully synthesized the target protein via amber suppression and were shown to be orthogonal to the fungal translation system. By replacing the wild-type Ec.TyrRS with a mutant with a higher affinity for the UAA O -methyl-L-tyrosine, the fungal system was able to initiate the synthesis of the UAA-labeled protein (UAA-protein). We further increased the expression level of the UAA-protein through several rational modifications. The successful development of a genetic code expansion technique for A. nidulans has introduced a potentially valuable approach to the study of fungal protein structure and function. • Amber suppression in A. nidulans requires the exogenous amber suppressor. • E. coli tRNATyr CUA /Tyr-tRNA synthetase incorporates unnatural amino acids in fungus. • Increasing tRNA transcription improves unnatural amino acid incorporation efficiency in fungus. [ABSTRACT FROM AUTHOR]

A new alkaloid named aspergilalkaloid A (1) with pyridoindole hydroxymethyl piperazine dione structure along with six known compounds 2-7 were isolated from deep-sea derived fungus Aspergillus sp. HDN20-1401. The structure including absolute configuration was elucidated by extensive NMR analyses, HRESIMS, ECD calculation, and theoretical NMR calculation with DP4+ analysis. All isolated compounds were tested for antimicrobial and anticancer activity. Aspergilalkaloid A (1) showed inhibitive activity against Bacillus cereus with MIC value of 12.5 μM and weak activity against MRCNS. [ABSTRACT FROM AUTHOR]

COVID-19 associated pulmonary aspergillosis (CAPA) had been reported, and raised concern about this secondary infection due to the high mortality. This study aimed to investigate the risk factors for CAPA. The enrolled 114 COVID-19 patients were further divided into CAPA group and non-CAPA group. Demographic characteristics, underlying diseases, laboratory parameters and therapeutic schedule between the two groups were compared to identify the independent risk factors for CAPA by univariate analysis and multivariable logistic regression analysis. Sensitivity and specificity of independent risk factors were confirmed by receiver operating characteristic (ROC) curve analysis. Univariate analysis showed that renal transplant, IL-6 and CRP levels, decreased CD4 + T cell and CD8 + T cell, duration of antibiotics therapy, and prolonged mechanical ventilation were risk factors for development of CAPA. These factors were further analyzed by multivariable logistic regression analysis and the results indicated that elevated IL-6 level, decreased CD4 + T cell and prolonged mechanical ventilation could be recognized as independent risk factors for CAPA in COVID-19 patients. Identification of these risk factors is essential to initiate antifungal therapy as soon as possible to improve outcome of patients with CAPA. [ABSTRACT FROM AUTHOR]

Fungal pathogens exhibit extensive strain heterogeneity, including variation in virulence. Whether closely related non-pathogenic species also exhibit strain heterogeneity remains unknown. Here, we comprehensively characterized the pathogenic potentials (i.e., the ability to cause morbidity and mortality) of 16 diverse strains of Aspergillus fischeri, a non-pathogenic close relative of the major pathogen Aspergillus fumigatus. In vitro immune response assays and in vivo virulence assays using a mouse model of pulmonary aspergillosis showed that A. fischeri strains varied widely in their pathogenic potential. Furthermore, pangenome analyses suggest that A. fischeri genomic and phenotypic diversity is even greater. Genomic, transcriptomic, and metabolic profiling identified several pathways and secondary metabolites associated with variation in virulence. Notably, strain virulence was associated with the simultaneous presence of the secondary metabolites hexadehydroastechrome and gliotoxin. We submit that examining the pathogenic potentials of non-pathogenic close relatives is key for understanding the origins of fungal pathogenicity. Examination of Aspergillus fischeri, a non-pathogenic close relative of the major fungal pathogen Aspergillus fumigatus, revealed extensive strain heterogeneity in virulence and identified an association with specific metabolic differences. [ABSTRACT FROM AUTHOR]

Marine-derived Aspergillus sp. strain w2-13, isolated from Dongshan Island in Fujian Province, produced five compounds through solid-state fermentation. This included a new polyketide, aspilactonol J (1), and four previously identified compounds (2-5). The structure of the new compound was determined using NMR, HRMS, and ECD, supported by theoretical calculations. A plausible biosynthetic pathway for polyketides 1-3 was also proposed. Cytotoxicity tests on various cancer cell lines revealed that aspilactonol J (1) exhibited significant selectivity and efficacy, especially against HepG2 cells, suggesting its potential for pharmaceutical development. This study highlights the role of marine fungi as valuable sources of bioactive natural products with therapeutic potential. [ABSTRACT FROM AUTHOR]

In this study, water samples were collected from four locations: a well, a tap, the Kharazi Valley, and the Tigris River. Samples were taken over three months--February, March, and April--and the following measurements were recorded: pH, TDS (Total dissolved solids), and temperature. The temperature of each water sample, measured during collection, ranged between 16°C and 25°C. The pH ranged from 7.3 to 8.8, while TDS reached the highest value in the river sample at 830, and for the other samples, a range between 221 and 360 was recorded. The samples were then inoculated on corn meal agar (CMA). In February, Penicillium spp. was the most prominent fungus, appearing in 62% of samples. In March, the yeast Candida spp. was the most common at 36%, and in April, Candida spp. remained prevalent, followed by Penicillium spp. at 26%, Fusarium spp. at 24%, and Aspergillus flavus, which appeared in samples collected from the Kharazi Valley. [ABSTRACT FROM AUTHOR]

Aspergillus flavus, a fungus known for producing aflatoxins, poses significant threats to agriculture and global health. Flavonoids, plant-derived compounds, inhibit A. flavus proliferation and mitigate aflatoxin production, although the precise molecular and physical mechanisms underlying these effects remain poorly understood. In this study, we investigated three flavonoids—apigenin, luteolin, and quercetin—applied to A. flavus NRRL 3357. We determined the following: (1) glycosylated luteolin led to a 10% reduction in maximum fungal growth capacity; (2) quercetin affected cell wall integrity by triggering extreme mycelial collapse, while apigenin and luteolin caused peeling of the outer layer of cell wall; (3) luteolin exhibited the highest antioxidant capacity in the environment compared to apigenin and quercetin; (4) osmotic stress assays did not reveal morphological defects; (5) flavonoids promoted cell adherence, a precursor for biofilm formation; and (6) RNA sequencing analysis revealed that flavonoids impact expression of putative cell wall and plasma membrane biosynthesis genes. Our findings suggest that the differential effects of quercetin, luteolin, and apigenin on membrane integrity and biofilm formation may be driven by their interactions with fungal cell walls. These insights may inform the development of novel antifungal additives or plant breeding strategies focusing on plant-derived compounds in crop protection. [ABSTRACT FROM AUTHOR]

Background: Invasive aspergillosis (IA) is a significant cause of morbidity and mortality in patients with haematological malignancies. Accurate diagnosis of IA is challenging due to non-specific symptoms and the impact of antifungal prophylaxis on biomarker sensitivity. Methods: This retrospective study evaluated the diagnostic performance of three serum biomarkers: Aspergillus Galactomannan Ag VirClia Monotest® (VirClia), Wako β-D-Glucan Test® (Wako BDG), and MycoGENIE Real-Time PCR® (MycoGENIE PCR). True positives were defined as patients with proven or probable IA (n = 14), with a positive Platelia Aspergillus Antigen® (Platelia) serving as a mycological criterion. True negatives were identified as patients with a positive Platelia assay but classified as non-probable IA (n = 10) and outpatients who consistently tested negative with the Platelia test throughout the study period (n = 20). Results: Most patients diagnosed with proven or probable IA were acute myeloid leukaemia or myelodysplastic syndrome patients receiving mould-active antifungal prophylaxis or treatment (71%). VirClia demonstrated high sensitivity (100%) for detecting IA, with a specificity of 83%. Wako BDG and MycoGENIE PCR showed lower sensitivities for IA (57% and 64%, respectively). MycoGENIE PCR detected Aspergillus spp. and Mucorales in two patients. Conclusions: Accurate diagnosis of IA remains challenging, especially in patients who have received mould-active antifungal treatment. VirClia showed comparable performance to Platelia, suggesting its potential for routine use. However, Wako BDG and MycoGENIE PCR results were less favourable in our study cohort. Nevertheless, MycoGENIE PCR detected two probable co-infections with Aspergillus spp. and Mucorales. [ABSTRACT FROM AUTHOR]

Three new meroterpenoids, asperinsuterpenes A–C (1–3), and eight previously reported natural products, namely asnovolin I (4), (2′E,4′E,6′E)-6-(1′-carboxyocta-2′,4′,6′-triene)-9-hydroxydrim-7-ene-11,12-olide (5), (2′E,4′E,6′E)-6-(1′-carboxyocta-2′,4′,6′-triene)-11,12-epoxy-9,11-dihydroxydrim-7-ene (6), cinereain (7), carnequinazolines A and B (8 and 9), carnemycin B (10), and stromemycin (11) were isolated from the fungus Aspergillus insuetus, strain BTBU20220155. The structures of the compounds were determined based on spectroscopic techniques, including 1D and 2D NMR, HRESIMS, and ECD experiments. The in vitro antimicrobial evaluation revealed that compounds 5 and 11 exhibited inhibitory activity against Candida albicans, with minimum inhibitory concentration (MIC) values of 12.5 and 25 μg/mL, respectively. These findings suggest that A. insuetus is a promising source of bioactive natural products with potential applications in antifungal therapy. [ABSTRACT FROM AUTHOR]

Observational studies indicate that Aspergillus colonization and allergic bronchopulmonary aspergillosis (ABPA) in people with cystic fibrosis (CF) are associated with poorer lung health and increased disease severity. We performed a longitudinal observational cohort study to analyse long-term outcomes of Aspergillus colonization and ABPA in children with CF. Anonymised UK CF Registry data from 2009 to 2019 for patients aged 8–17 years in 2009–2010 were collected. For the baseline cohort analysis, patients were classified based on the presence of Aspergillus colonization and ABPA in 2009 and/or 2010. For the longitudinal analysis, patients were categorised according to annual Aspergillus colonization and ABPA status. Comparisons made were (1) Aspergillus positive vs. negative; (2) excluding those with ABPA: Aspergillus positive vs. negative; and (3) ABPA positive vs. negative. Primary outcome was percentage predicted FEV1 decline and secondary outcomes included BMI decline, mortality, lung transplant, and IV antibiotic use. Of the 1675 children, 263 had Aspergillus colonization in the baseline cohort, 260 were diagnosed with ABPA, and 80 had both. Baseline cohort analysis showed significantly lower lung function (p < 0.0001) and increased antibiotic treatment (p < 0.001) in those with Aspergillus colonization and in those with ABPA. Longitudinal analysis showed ABPA was associated with increased decline in lung function (p < 0.00001) and BMI (p < 0.00001). Aspergillus colonization was associated with increased decline in BMI (p = 0.005) but not lung function (p = 0.30). ABPA was associated with increased decline in long-term lung function and BMI in children and young people with CF. Aspergillus colonization was associated with lower lung function at baseline, but no increased rate of decline was observed long-term. [ABSTRACT FROM AUTHOR]

The endolichenic fungus Aspergillus sp. was isolated from the lichen Xanthoparmelia conspersa harvested in France. Aspergillus sp. was grown on a solid culture medium to ensure the large-scale production of the fungus with a sufficient mass of secondary metabolites. The molecular network analysis of extracts and subfractions enabled the annotation of 22 molecules, guiding the purification process. The EtOAc extract displayed an antiproliferative activity of 3.2 ± 0.4 µg/mL at 48 h against human colorectal cancer cells (HT-29) and no toxicity at 30 µg/mL against human triple-negative breast cancer (TNBC) cells (MDA-MB-231) and human embryonic kidney (HEK293) non-cancerous cells. Among the five prenylated compounds isolated, of which four are echinulin derivatives, compounds 1 and 2 showed the most important activity, with IC50 values of 1.73 µM and 8.8 µM, respectively, against HT-29 cells. [ABSTRACT FROM AUTHOR]