Aspergillus Species Research Articles

The Underrepresented Quinolinone Alkaloids in Genera Penicillium and Aspergillus: Structure, Biology, and Biosynthetic Machinery.

Quinolone alkaloids are N-heterocycles with extensive structural diversity, mainly derived from in fungi from anthranilic acid and amino acids as precursors with a wide range of biological activities as antifungal, antimicrobial, anti-inflammatory, and insecticidal activities. The quinolone basic skeleton comprised of either 2-quinolones or 4-quinolones generated more than one hundred compounds. Several reviews discussed quinolones; particularly, the fluoroquinolones, yet few studies tackled natural quinolones. Many of these quinolones were not assayed for their antimicrobial potential despite their unique stereospecificity, which can supersede synthetic quinolones if their discovery is coupled with OMICS techniques, biochemical and molecular strategies as heterologous expression to maximize their yield. Herein, we conducted a comprehensive review of the quinolone's family in Aspergillus and Penicillium species, the exclusive producers of quinolones whether they are soil, endophytic or marine derived highlighting their isolation, chemical structures, pharmacological effects, structure activity relationships if any, and biosynthetic machinery. We believe that our initiative will pave the way for further development of natural quinolones as future antimicrobial agents.

Phospholipid dynamics in Aspergillus species: relations between biological membrane composition and cellular morphology.

Biological membranes, primarily composed of phospholipid bilayers, are essential structures that compartmentalize the cell from the extracellular environment. The biosynthesis and regulation of membrane lipids have been extensively studied in model organisms such as Saccharomyces cerevisiae and mammalian cells. However, our understanding of biological membrane regulation in filamentous fungi, some of which are significant in medicine, pharmacy, and agriculture, remains limited. This minireview provides a comprehensive overview of the latest knowledge, focusing on filamentous fungi of Aspergillus species. Recent progress in understanding dynamic changes in membrane lipid profiles, driven by improvements in analytical techniques for lipidomics, is also presented. Furthermore, known that the cell morphology of filamentous fungi is closely linked to its harmful and beneficial characteristics, the influence of membrane composition on cell morphology is discussed. The integration of these findings will further enhance our understanding of the biological functions of membranes in filamentous fungi.

Efficient biosorption of Zn(II), Cd(II), and Pb(II) by Aspergillus brasiliensis in industrial wastewater coupled with electrochemical monitoring via sensor enhanced with modified silver nanoparticles.

This work investigates the use of Aspergillus brasiliensis, this particular species of Aspergillus, as a biosorbent for the first time. It is employed to biosorption Zn(II), Cd(II), and Pb(II) and combines the biosorption experiments with electrochemical measurements for in situ analysis. For the experiments, a batch system was employed with the dead biomass. In order to determine the biosorption capacity, the impact of several operational parameters was examined, including pH, temperature, agitation speed, contact time, and initial metal concentration, and the optimum values were 5, 30°C, 150rpm, 2h, and 150ppm, respectively. Using 0.2g biomass in 100mL solution, the maximal uptake of Zn(II), Cd(II), and Pb(II) at ideal conditions was determined to be 33.67, 24.51, and 36.76, respectively. The Langmuir and Freundlich isotherm model was studied for the biosorption process. An electrochemical sensor using nanomaterials is designed and constructed to monitor the concentration of these metals. The silver nanoparticles functionalized with thiosemicarbazide and 6-mercaptohexanoic acid (mercaptohexanoylhydrazinecarbothioamide-coated silver nanoparticles, MHHC-AgNPs) linked to the carboxylated multi-walled carbon nanotubes (MWCNTs) were utilized for glassy carbon electrode modification (MHHC-AgNPs/MWCNTs/GCE). The concentration range of Zn(II) is 0.7-173µg/L, Cd(II) is 1.18-293µg/L, and Pb(II) is 2.17-540µg/L. The detection limits for Zn(II), Cd(II), and Pb(II) are 0.036µg/L, 0.15µg/L, and 0.16µg/L, respectively. Under optimized conditions, these results were obtained using the differential pulse anodic stripping voltammetry method (DPASV). The successful detection of Zn(II), Cd(II), and Pb(II) was achieved by effectively preventing interference from other common ions. It was effectively employed for measuring ions in industrial wastewater, and the results obtained aligned with those acquired from an atomic absorption spectrometer (AAS). Thus, Aspergillus brasiliensis species, along with this electrochemical sensor, can be used to remediate and monitor environmental pollution, Zn(II), Cd(II), and Pb(II), successfully.

Clinical applications of immunoglobulin G against different individual Aspergillus species for the diagnosis of chronic pulmonary aspergillosis among at-risk populations

ABSTRACT Aspergillus fumigatus-specific IgG is often used as a diagnostic test for chronic pulmonary aspergillosis (CPA), but few studies have evaluated the performance and serology of IgGs from species other than A. fumigatus. In this study, we evaluated the serology and performance of different Aspergillus species-specific IgG antibodies in patients with CPA and at-risk populations and whether different Aspergillus species-specific IgGs could be of clinical utility and aid in the diagnosis of CPA caused by all Aspergillus species. A total of 187 participants were included between 2020 and 2022 (12 with CPA, 75 with old tuberculosis [TB], 45 with active TB and 55 with bronchiectasis). We measured the serum Aspergillus fumigatus, flavus, terreus, niger-specific, and mixed Aspergillus IgG levels (Phadia ImmunoCap). The correlation was the strongest between A. fumigatus and A. niger (Spearman’s rank: 0.940), followed by A. niger and A. flavus (Spearman’s rank: 0.915). A. terreus-specific IgG was less strongly correlated with the other three Aspergillus species-specific IgG (Spearman’s rank: 0.828–0.849). A. flavus (4 of 6, 67%) was the dominant species. Using the at-least-one-positive approach, the highest performance was obtained when A. fumigatus and A. flavus IgGs were used (sensitivity, 0.75; specificity, 0.84). Significant cross-reactivity exists among different Aspergillus-species IgGs although the correlation may be less significant for A. terreus. In addition to the commonly used A. fumigatus IgG test, IgGs specific to local prevalent Aspergillus species may provide additional clinical utility.

Development of a whole-cell SELEX process to select species-specific aptamers against Aspergillus niger

BackgroundSpores produced by the filamentous fungus Aspergillus niger are abundant in a variety of environments. The proliferation of this fungus in indoor environments has been associated to health risks and its conidia can cause allergic reaction and severe invasive disease in animals and humans. Therefore, the detection and monitoring of Aspergillus conidia is of utmost importance to prevent serious fungal infections and contaminations. Among others, aptamers could serve as biosensors for the specific detection of fungal spores.ResultsIn this study, DNA aptamers specific to conidia of A. niger were developed by optimizing a whole-cell SELEX approach. Three whole-cells SELEX experiments were performed in parallel with similar conditions. Quantification of recovered ssDNA and melting curve analyses were applied to monitor the ongoing SELEX process. Next-generation sequencing was performed on selected recovered ssDNA pools, allowing the identification of DNA aptamers which bind with high affinity to the target cells. The developed aptamers were shown to be species-specific, being able to bind to A. niger but not to A. tubingensis or to A. nidulans. The binding affinity of two aptamers (AN01-R9-006 and AN02-R9-185) was measured to be 58.97 nM and 138.71 nM, respectively, which is in the range of previously developed aptamers.ConclusionsThis study demonstrates that species-specific aptamers can be successfully developed via whole-cell SELEX to distinguish different Aspergillus species and opens up new opportunities in the field of diagnostics of fungal infections.

Outcomes in hematopoetic cell transplantation in the setting of mold infections in patients with chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a disorder of immunity characterized by phagocyte dysfunction. Mold infections in patients with CGD are often severe and disseminated. We present patient characteristics, microbiological data, and outcomes for 26 patients with CGD who received hematopoietic cell transplantation (HCT) or gene therapy-modified cells (GT) between 2008 and 2019, with proven fungal infection either before or during their transplant. All patients engrafted, and all but one GT recipient had neutrophil recovery and evidence of functional correction. Eighteen patients (69%) are currently alive and 19 patients (73% of total, 90% of patients with repeat imaging performed) had evidence of radiographic improvement. With 3 exceptions, deaths were not principally related to the fungal infection and duration of antecedent infection did not correlate with death. Aspergillus species accounted for the majority of disease (50%), followed by Phellinus species (18%). Osteomyelitis and disseminated disease were common, as only 11 patients (42%) had disease restricted to pneumonia. Triazole therapy was used in all 26 patients, with combination therapy used in 25 (96%). HCT or gene therapy, with appropriate antifungal therapy, are viable therapies for refractory fungal infections in patients with CGD.

Revisiting Aspergillus terreus MTCC6324 recombinant alcohol oxidase (rAOx): enhanced in-silico insight into structure, function, and substrate sequestration mechanism

Alcohol oxidase (AOx) enzymes have gained significant attention for their potential in industrial applications due to their unique ability to catalyze irreversible oxidation of diverse alcohol substrates without external co-factors. This study revisits and enhances in-silico work on Aspergillus terreus MTCC6324 recombinant AOx (rAOx) enzyme, combining artificial intelligence (AlphaFold), molecular docking (AutoDock Vina) techniques and Molecular dynamics (MD) simulations (Desmond). Comprehensive sequence analysis revealed a high degree of conservation among 23 AOx amino acid sequences from various Aspergillus species highlights conserved regions, affirming its GXGXXG Rossmann fold motif. AlphaFold-predicted 3D structure of rAOx demonstrated improved stereo-chemical stability compared to I-TASSER predicted structure with 87.6% amino acid residues in most favourable region of Ramachandran plot compared to 79.5%, respectively. Molecular docking revealed the binding affinities of co-factors FAD and diverse alcohol substrates, with cinnamyl alcohol exhibiting robust interaction with rAOx holoenzyme. MD simulations further elucidate the stability and dynamics of rAOx-FAD-cinnamyl alcohol complex over 100 nanoseconds. The simulations showcase FAD’s stable binding within the protein core and highlights transient substrate interactions, dissociating within the active site after 75 ns suggesting a substrate sequestration mechanism. The study unveils substrate sequestration mechanism wherein cinnamyl alcohol exhibits temporary binding, leading to quick detachment from active site, mimicking reported exponential kinetics. This study not only validates previous findings but also offers a comprehensive understanding of intricate dynamics governing rAOx enzymatic activity. The improved sequence-to-structure prediction and detailed molecular insights into substrate sequestration provide a valuable foundation for future experimental investigations and rational design of bio-catalytic processes.

The Inhibitory Activity of Salicylaldehyde Compounds on Aspergillus Species and Their Effects on Aflatoxin Production and Crop Seed Germination

The Inhibitory Activity of Salicylaldehyde Compounds on Aspergillus Species and Their Effects on Aflatoxin Production and Crop Seed Germination

Versatile Xylose and Arabinose Genetic Switches development for Yeasts

Inducible transcription systems are essential tools in genetic engineering, where tight control, strong inducibility and fast response with cost-effective inducers are highly desired. However, existing systems in yeasts are rarely used in large-scale fermentations due to either cost-prohibitive inducers or incompatible performance. Here, we developed powerful xylose and arabinose induction systems in Saccharomyces cerevisiae, utilizing eukaryotic activators XlnR and AraRA from Aspergillus species and bacterial repressors XylR and AraRR. By integrating these signals into a highly-structured synthetic promoter, we created dual-mode systems with strong outputs and minimal leakiness. These systems demonstrated over 4000- and 300-fold regulation with strong activation and rapid response. The dual-mode xylose system was fully activated by xylose-rich agricultural residues like corncob hydrolysate, outperforming existing systems in terms of leakiness, inducibility, dynamic range, induction rate, and growth impact on host. We validated their utility in metabolic engineering with high-titer linalool production and demonstrated the transferability of the XlnR-based xylose induction system to Pichia pastoris, Candida glabrata and Candida albicans. This work provides robust genetic switches for yeasts and a general strategy for integrating activation-repression signals into synthetic promoters to achieve optimal performance.

Pulmonary Aspergillosis: An Observation from a Tertiary Care Hospital of Western Uttar Pradesh

Background: Aspergillus is the most frequently occurring fungal infection in immunocompromised patients with a high mortality rate. Invasive pulmonary aspergillosis is the most serious entity on the spectrum of pulmonary aspergillosis. Limited studies on the occurrence of pulmonary aspergillosis from this geographical area prompted us to carry out this study. Materials and Methods: This hospital-based cross-sectional observational study was carried out in the Postgraduate Department of Microbiology of a tertiary care medical teaching hospital in western Uttar Pradesh for one year. A total of 1032 respiratory samples were subjected for isolation and identification of fungal pathogens by direct microscopic examination (KOH mount) and culture on Sabouraud dextrose agar. Results: The isolation rate of pulmonary aspergilli was 6.97%. The majority of the respiratory samples received were sputum 900 (87.2%) followed by bronchoalveolar lavage fluid 132 (12.7%). The pulmonary pathology was predominantly seen in the age group of 41–50 years (25%). Male patients (69%) were predominant. The majority of the samples (50%) were from the respiratory medicine ward followed by the respiratory medicine ICU (25%). Aspergillus fumigatus (58%) was the predominant species isolated followed by Aspergillus flavus (25%). Conclusion: Isolation of Aspergillus species from patients of pulmonary pathology needs to be correlated clinically to rule out colonization as they may need proper antifungal treatment. Indiscriminate use of antifungals may lead to the emergence of antifungal drug resistance.

Genomic Assessment of Resistance of Invasive Fungal Infections in Immunocompromised Patients

Introduction: Invasive fungal infections (IFIs) are emerging and significantly increased in immunocompromised populations. These infections are the most commonly acquired by inhalation of spores and can be transmitted by percutaneous inoculation in cutaneous and subcutaneous infections. Candida and Aspergillus species remain the most common cause of invasive fungal infections including neutropenia, hematological malignancies, bone marrow transplantation, parenteral nutrition prolonged treatment with corticosteroids, chemotherapy, HIV infection, invasive medical procedures, and the newer immune suppressive agents. Materials and Methods: An observational study was carried out at SRM MCH&RC, Tamil Nadu, India, in January 2020. Invasive fungal infections were identified in conventional methods (KOH, Gram staining, culture, sugar assimilation, sugar fermentation, LPCB). Antifungal susceptibility testing was done as per standard guidelines; the resistant species were subjected to molecular testing to identify the gene. Results: Clinical samples are collected from the various departments (blood, pus, tissues, BAL, pleural fluid, and other body fluids). Out of 110 clinical samples, 16 samples were positive for yeast infections and five were positive for moulds. Eighty-nine samples were negative for fungal infection. Among yeast isolates, Candida tropicalis (37%) was the most common in the study population, followed by C albicans (25%), C krusei (19%), C.glabrata (13%), and C.parapsilosis (6%). Among the filamentous fungi, all the isolates were present in the same prevalence. Some of the Candida spp. were found to be resistant to amphotericin B (2), fluconazole (2), and itraconazole (1). All moulds were found to be sensitive to the tested antifungals by microbroth dilution methods. Among the resistant Candida, spp.ERG11 gene was found to be common. Conclusion: We observed that the early detection of etiological agents by microscopy and culture and prompt initiation of antifungal therapy can aid in the reduction of morbidity and mortality among immunocompromised patients.

HALOPHILIC ASPERGILLUS SPECIES IN EXTREME ENVIRONMENTS: PHYSIOLOGY, ADAPTATIONS, AND APPLICATIONS

Salt is essential for growth at certain limits, but life dwelling in harsh, salty environments are the halophiles. Studies on the halophilic bacteria, archaea, and fungi are reported around different locations, but the fungus Aspergillus species is a predominant halophilic eukaryote reported in various research works. They have been reported from an environment with high salt concentrations. Halophilic Aspergillus species grow better in harsh conditions and have an exciting opportunity for research and application ahead of them. Their potential in biotechnology, together with their special capacity for adaptation to harsh settings, makes them precious in many sectors from environmental science, to biotechnology, and even in bioremediation settings. Therefore, this work review the physiology and unique adaptations of halophilic Aspergillus species in extreme environments, biomolecule produces and their applications in different areas and future prospects.

Acute Toxicity of Mycotoxigenic Fungi Isolates in Ready-to-Eat Meat in Buea, Cameroon

Introduction: Meat is an important source of nutrition for many people worldwide. Away from homes, it is widely consumed in restaurants (e.g. small roadside) and non-restaurants (including drinking parlors and open-air)in various forms assnack. Objective: This paper reports on the acute toxicity of mycotoxigenic fungi isolates from various ready-to-eat meat from Buea, Cameroon. Method: Ten varieties of ready-to-eat meat samples (N=130: raw beef (n=18), beef soya (n=29), fried chicken (n=11), chicken soya (n=10), snail soya (n=13), fried pork (n=06), fried cow liver (n=13), roasted goat (n=06), boiled cow skin (n=07) and smoked beef (n=17).were collected from Buea municipality. The samples were cultures, and fungal isolates isolated microscopically. Thereafter, an acute toxicity test using 24 young BALB/c mice (weight range: 22-25g) was performed. Results: A total of 40 mycotoxigenic fungi belonging to five genera (Aspergillus, Penicillium, Fusarium, Rhizomucor, and Rhizopus) were identified. The most dominant species was Aspergillus (unidentified Aspergillus species, 23.1%; and Aspergillus ochraceus,10.3%).The order of Aspergillus fungi proliferation were roasted goat liver(20%), fried chicken (20%), snails soya (20%)ean body weight of test mice significantly decreased (p<0.05) after the first 7 days of feeding with a mycotoxigenic fungi-supplemented diet relative to control mice that ate healthy diets. Aspartate Transaminase (AST, range: 169.9-563.1U/L) and Alanine Transaminase (ALT, range:521.1-707.5U/L) levels were significantly (p<0.05) higher than the reference values for healthy mice (range: 60-100U/L for AST and 25-6U/L for ALT). Conclusion: Given the toxicity potentials of mycotoxigenic fungi, e.g. production of toxic secondary metabolites, not reported in this paper, and demonstrated by the liver toxicity/function test, ready-to-eat meat in Buea, Cameroon may not be adequately safe for consumption.

Transcriptome analysis of Ochratoxin a (OTA) producing Aspergillus westerdijkiae fc-1 under varying osmotic pressure

ABSTRACT Ochratoxin A (OTA) is a toxic secondary metabolite produced by the Aspergillus species which can contaminate various food products. This study analysed the transcriptome of the Aspergillus westerdijkiae fc-1 strain under NaCl concentrations of 0, 20, and 100 g/L using RNA-Seq technology to examine gene transcriptional changes linked to osmotic stress and OTA production. Significant changes were observed in metabolic-pathways associated with carbohydrates, cellular communication, and hydrolase activity under 20 g/L NaCl. The HOG1 gene, associated with osmotic pressure regulation was down-regulated by 78.06%. In contrast, OTA biosynthesis genes otaA, otaB, and otaC were up-regulated by 3.26 fold, 1.99 fold, and 2.06 fold, respectively. Conversely, the otaD gene was down-regulated by 43.50%. At 100 g/L NaCl, pathways related to ion transport, peptide metabolism, ribosomal function, and transmembrane transporter protein activities were significantly up-regulated. The HOG1 gene was up-regulated by 28.32% and OTA biosynthesis genes otaA, otaB, otaC, and otaD showed up-regulation of 27.06%, 36.80%, 19.59%, and 5.72 fold, respectively. The study highlights the role of metabolic pathways in osmotic stress regulation and the correlations between HOG1 expression and OTA biosynthesis genes, providing insights for developing strategies to prevent OTA contamination in food.

Evaluation of the Activity of Triazoles Against Non-fumigatus Aspergillus and Cryptic Aspergillus Species Causing Invasive Infections Tested in the SENTRY Program.

The activity of isavuconazole and other triazoles against non-fumigatus (non-AFM) Aspergillus causing invasive aspergillosis was evaluated. A total of 390 non-AFM isolates were collected (1/patient) in 2017-2021 from 41 hospitals. Isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry and/or internal spacer region/β-tubulin sequencing and tested by Clinical and Laboratory Standards Institute (CLSI) broth microdilution. CLSI epidemiological cutoff values were applied, where available. Isavuconazole showed activity against Aspergillus sections Flavi (n = 122; minimum inhibitory concentration [MIC]50/90, 0.5/1 mg/L), Terrei (n = 57; MIC50/90, 0.5/0.5 mg/L), Nidulantes (n = 34; MIC50/90, 0.12/0.25 mg/L), Versicolores (n = 7; MIC50, 1 mg/L), and Circumdati (n = 2; MIC range, 0.12-2 mg/L). Similar activity was displayed by other triazoles against those Aspergillus sections. Most of the isolates from Aspergillus sections Fumigati (n = 9), Nigri (n = 146), and Usti (n = 12) exhibited elevated MIC values to isavuconazole (MIC50/90, 2/-, 2/4, and 2/8 mg/L), voriconazole (MIC50/90, 2/-, 1/2, and 4/8 mg/L), itraconazole (MIC50/90, 2/-, 2/4, and 8/>8 mg/L), and posaconazole (MIC50/90, 0.5/-, 0.5/1, and >8/>8 mg/L), respectively. Isavuconazole was active (MIC values, ≤1 mg/L) against Aspergillus parasiticus, Aspergillus tamarii, Aspergillus nomius, Aspergillus nidulans, Aspergillus unguis, Aspergillus terreus, Aspergillus alabamensis, and Aspergillus hortai, while isavuconazole MIC values between 2 and 8 mg/L were observed against cryptic isolates from Aspergillus section Fumigati. Isavuconazole inhibited 96.1% of Aspergillus niger and 80.0% of Aspergillus tubingensis at ≤4 mg/L, the CLSI wild-type cutoff value for A niger. Voriconazole, itraconazole, and posaconazole showed similar activity to isavuconazole against most cryptic species. Isavuconazole exhibited potent in vitro activity against non-AFM; however, the activity of triazoles varies among and within cryptic species.

FREQUENCY OF ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS (ABPA) IN PATIENTS ADMITTED WITH ACUTE EXACERBATION OF ASTHMA IN A TERTIARY CARE HOSPITAL IN KARACHI: A PROSPECTIVE OBSERVATIONAL STUDY

Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus species and often complicates the clinical course of asthma, leading to more severe exacerbations and poor disease control. Despite its clinical relevance, the prevalence of ABPA in asthma patients remains under-reported, especially in developing countries like Pakistan. Objective: This study aimed to determine the prevalence of ABPA among patients admitted with acute exacerbations of asthma at a tertiary care hospital in Karachi, Pakistan. Methods: A prospective observational quantitative study was conducted at the Department of Pulmonary Medicine, Aga Khan Hospital University Karachi, Pakistan from January 2023 to December 2023 in Karachi. The study included 150 isolated patients of either gender, aged between 18 and 80 years, with a clinical diagnosis of asthma or those eligible for spirometry. Data collected included demographic details, past medical history, pulmonary function test results, and serological data for ABPA diagnosis. The presence of ABPA was confirmed by elevated serum total IgE concentration, specific IgE to Aspergillus fumigatus, and radiological findings. Statistical analysis was conducted using SPSS, with p-values < 0.05 considered statistically significant. Results: The study revealed an overall prevalence of ABPA in 20% of the 150 patients with acute asthma exacerbations. Serum total IgE concentration was significantly higher in the ABPA group (450 IU/mL) compared to the non-ABPA group (p < 0.05). Additionally, patients with ABPA had significantly lower FEV1 (60% predicted) compared to those without ABPA (p < 0.05). Conclusion: The study highlights a notable prevalence of ABPA among asthma patients experiencing acute exacerbations. This underscores the importance of raising clinical awareness and implementing timely diagnostic strategies for ABPA in asthma management, which could significantly improve patient outcomes.

Alligamycin A, an antifungal β-lactone spiroketal macrolide from Streptomyces iranensis

Fungal infections pose a great threat to public health and there are only four main types of antifungal drugs, which are often limited with toxicity, drug-drug interactions and antibiotic resistance. Streptomyces is an important source of antibiotics, represented by the clinical drug amphotericin B. Here we report the discovery of alligamycin A (1) as an antifungal compound from the rapamycin-producer Streptomyces iranensis through genome-mining, genetics and natural product chemistry approaches. Alligamycin A harbors a unique chemical scaffold with 13 chiral centers, featuring a β-lactone moiety, a [6,6]-spiroketal ring, and an unreported 7-oxo-octylmalonyl-CoA extender unit incorporated by a potential crotonyl-CoA carboxylase/reductase. It is biosynthesized by a type I polyketide synthase which is confirmed through CRISPR-based gene editing. Alligamycin A displayed potent antifungal effects against numerous clinically relevant filamentous fungi, including resistant Aspergillus and Talaromyces species. β-Lactone ring is essential for the antifungal activity since alligamycin B (2) with disruption in the ring abolished the antifungal effect. Proteomics analysis revealed alligamycin A potentially disrupts the integrity of fungal cell walls and induces the expression of stress-response proteins in Aspergillus niger. Discovery of the potent antifungal candidate alligamycin A expands the limited antifungal chemical space.

Genomic Localization Bias of Secondary Metabolite Gene Clusters and Association with Histone Modifications in Aspergillus.

Fungi are well-known producers of bioactive secondary metabolites (SMs), which have been exploited for decades by humankind for various medical applications like therapeutics and antibiotics. SMs are synthesized by biosynthetic gene clusters (BGCs)-physically co-localized and co-regulated genes. Because BGCs are often regulated by histone post-translational modifications (PTMs), it was suggested that their chromosomal location is important for their expression. Studies in a few fungal species indicated an enrichment of BGCs in sub-telomeric regions; however, there is no evidence that BGCs with distinct genomic localization are regulated by different histone PTMs. Here, we used 174 Aspergillus species covering 22 sections to determine the correlation between BGC genomic localization, gene expression, and histone PTMs. We found a high abundance and diversity of SM backbone genes across the Aspergillus genus, with notable unique genes within sections. Being unique or conserved in many species, BGCs showed a strong bias for being localized in low-synteny regions, regardless of their position in chromosomes. Using chromosome-level assemblies, we also confirmed a significantly biased localization in sub-telomeric regions. Notably, SM backbone genes in sub-telomeric regions and about half of those in low-synteny regions exhibit higher gene expression variability, likely due to the similar higher variability in H3K4me3 and H3K36me3 histone PTMs; while variations in histone H3 acetylation and H3K9me3 are not correlated to genomic localization and expression variation, as analyzed in two Aspergillus species. Expression variability across four Aspergillus species further supports that BGCs tend to be located in low-synteny regions and that regulation of expression in those regions likely involves different histone PTMs than the most commonly studied modifications.

Evaluation of metagenomic next-generation sequencing (mNGS) combined with quantitative PCR: cutting-edge methods for rapid diagnosis of non-invasive fungal rhinosinusitis.

Fungal rhinosinusitis is a significant and growing health concern in arid regions, with an increasing incidence over recent decades. Without timely and appropriate management, it can lead to severe complications, including potential intracranial spread. This study aims to establish efficient and rapid diagnostics for non-invasive fungal rhinosinusitis (FRS), addressing the challenge of its difficult-to-culture diagnosis. Twenty-eight patients suspected of FRS were studied using endoscopic sinus surgery to obtain tissue samples for histopathology, direct microscopy, fungal culture, quantitative PCR (qPCR) and metagenomic next-generation sequencing (mNGS) detection. A patented qPCR targeting prevalent Aspergillus species was evaluated. The patient cohort had a male-to-female ratio of 9:14, with disease duration up to 50 years. Histopathologically, 23 out of 28 cases were positive. Fungal culture exhibited a sensitivity of 21.74%, with one false positive. qPCR and mNGS showed 100% sensitivity and specificity, with a 100% consistency rate for identification at the species level (23/23), and potential detection of cases with co-infections. The most common pathogen was A. flavus, followed by A. fumigatus and A. niger. Two cases involved mixed infections of A. fumigatus and A. flavus. qPCR and mNGS proved effective in rapidly identifying fungi from fresh sinus tissue that are challenging to culture, surpassing conventional methods. However, further evaluation and optimization with a larger cohort of patients are necessary. Histopathology is still recommended to confirm the clinical significance of the detected fungal species.

Exceptional Rarity Unveiled: Isolated Fungal Osteomyelitis of Great Toe by Fusarium Solani-Unprecedented Presentation and Exquisite Management Insights

Fungal osteomyelitis is a rare but significant condition, often associated with immunocompromised states or severe systemic illnesses. This condition involves fungal pathogens, primarily Aspergillus, Candida, and Mucor species. Among these, Aspergillus is the most commonly implicated, especially in cases of vertebral osteomyelitis, although fungal infections involving bones like the distal phalanx of the toe are rare. In particular, Fusarium solani, though less frequently reported, has gained recognition for its role in causing localized osteomyelitis in both immunocompetent and immunocompromised patients. A case involving a 57-year-old male with no significant history of immunosuppression is presented. The patient developed localized pain and swelling in the left toe following a minor traumatic injury. Initial radiographic imaging revealed bone erosion, leading to a diagnosis of osteomyelitis. Cultures from bone biopsy identified Fusarium solani as the causative pathogen. This is noteworthy as the fungus, though commonly found in soil, water, and plants, rarely infects bone structures. The patient was treated with a combination of antifungal therapy, including voriconazole and surgical debridement. The rarity of Fusarium solani osteomyelitis and its unusual presentation in an immunocompetent host adds to the complexity of diagnosing fungal infections in osteomyelitis. Treatment typically involves a multidisciplinary approach that combines both medical and surgical interventions. The case highlights the importance of considering fungal pathogens, even in unusual clinical settings, especially when initial treatments fail to provide resolution. Early diagnosis and targeted therapy can improve outcomes, particularly in cases involving uncommon fungal pathogens such as Fusarium solani. This report emphasizes the need for awareness of fungal osteomyelitis in immunocompetent individuals and underscores the critical role of fungal cultures and imaging studies in guiding management.