Aspergillus Fumigatus Species Research Articles

Exposure to resistant fungi across working environments and time

Antifungal resistance has emerged as a significant health concern with increasing reports of resistant variants in previously susceptible species. At present, little is known about occupational exposure to antifungal-resistant fungi. This study aimed to investigate Danish workers' occupational exposure to airborne fungi resistant to first-line treatment drugs. A retrospective study was performed on a unique collection of personal exposure samples gathered over a twenty-year period from Danish working environments, in sectors including agriculture, animal handling, waste management, and healthcare. A total of 669 samples were cultivated at 37 °C and fungal colonies were identified using MALDI-TOF MS. Subsequently, identification was confirmed by amplicon sequencing the genes of calmodulin and beta-tubulin to unveil potential cryptic species.Infectious fungi (495 isolates from 23 species) were tested for resistance against Itraconazole, Voriconazole, Posaconazole, and Amphotericin B. Working environments were highly variable in the overall fungal exposure, and showed vastly different species compositions. Resistance was found in 30 isolates of the species Aspergillus fumigatus (4 of 251 isolates), A. nidulans (2 of 13), A. niger complex (19 of 131), A. versicolor (3 of 18), and A. lentulus (2 of 2). Sequence analysis revealed several cryptic species within the A. niger complex including A. tubingensis, A. luchuensis, and A. phoenicis. Among the resistant A. fumigatus isolates, two contained the well-described TR34/L98H mutation in the cyp51A gene and promoter region, while the remainder harbored silent mutations.The results indicate that the working environment significantly contributes to exposure to resistant fungi, with particularly biofuel plant workers experiencing high exposure. Differences in the prevalence of resistance across working environments may be linked to the underlying species composition.

Fungal Colonization of the Airways of Patients with Cystic Fibrosis: the Role of the Environmental Reservoirs.

Filamentous fungi frequently colonize the airways of patients with cystic fibrosis and may cause severe diseases, such as the allergic bronchopulmonary aspergillosis. The most common filamentous fungi capable to chronically colonize the respiratory tract of the patients are Aspergillus fumigatus and Scedosporium species. Defining the treatment strategy may be challenging, the number of available drugs being limited and some of the causative agents being multiresistant microorganisms. The knowledge of the fungal niches in the outdoor and indoor environment is needed for understanding the origin of the contamination of the patients. In light of the abundance of some of the causative molds in compost, agricultural and flower fields, occupational activities related to such environments should be discouraged for patients with cystic fibrosis (CF). In addition, the microbiological monitoring of their indoor environment, including analysis of air and dust on surfaces, is essential to propose preventive measures aiming to reduce the exposure to environmental molds. Nevertheless, some specific niches were also identified in the indoor environment, in relation with humidity which favors the growth of thermotolerant molds. Potted plants were reported as indoor reservoirs for Scedosporium species. Likewise, Exophiala dermatitidis may be spread in the kitchen via dishwashers. However, genotype studies are still required to establish the link between dishwashers and colonization of the airways of CF patients by this black yeast. Moreover, as nothing is known regarding the other filamentous fungi associated with CF, further studies should be conducted to identify other potential specific niches in the habitat.

Analyzing the structure of the metal complexes of biologically active azo dye ligand

A novel azo dye ligand was created by diazotizing 4‐aminoantipyrine and then coupling it with 2‐aminophenol as part of a methodical investigation of physiologically active compounds, 4‐aminoantipyrine. The novel complexes containing Cr(III), Fe(III), Mn(II), Co(II), Ni(II), Zn(II), Cu(II), and Cd(II) were created from the target ligand (L). The structures of the ligand and metal complexes were verified by elemental analyses, thermogravimetric analysis–difference thermogravimetry (TGA‐DTG), conductivity measurements, infrared (IR), UV–Vis, 1H‐nuclear magnetic resonance (NMR), X‐ray diffraction (XRD), and mass spectrometry. Using the Gaussian 09 tool, the density functional theory (DFT)/B3LYP method was utilized to compute the energy gaps and other important theoretical features. Also, the newly synthesized azo dye ligand, in comparison with metal complexes, was screened for its antimicrobial activity. The crystal structures of Staphylococcus aureus and Bacillus subtilis as gram‐positive bacteria, Salmonella sp. and Escherichia coli as gram‐negative bacteria, and fungal (Aspergillus fumigatus and Candida albicans) species were compared with the produced azo dye and its metal complexes via molecular docking. Most of the complexes exhibited greater antimicrobial activities against these organisms than did the original azo dye ligand.

Identification of closely related species in Aspergillus through Analysis of Whole-Genome.

The challenge of discriminating closely related species persists, notably within clinical diagnostic laboratories for invasive aspergillosis (IA)-related species and food contamination microorganisms with toxin-producing potential. We employed Analysis of the whole-GEnome (AGE) to address the challenges of closely related species within the genus Aspergillus and developed a rapid detection method. First, reliable whole genome data for 77 Aspergillus species were downloaded from the database, and through bioinformatic analysis, specific targets for each species were identified. Subsequently, sequencing was employed to validate these specific targets. Additionally, we developed an on-site detection method targeting a specific target using a genome editing system. Our results indicate that AGE has successfully achieved reliable identification of all IA-related species (Aspergillus fumigatus, Aspergillus niger, Aspergillus nidulans, Aspergillus flavus, and Aspergillus terreus) and three well-known species (A. flavus, Aspergillus parasiticus, and Aspergillus oryzae) within the Aspergillus section. Flavi and AGE have provided species-level-specific targets for 77 species within the genus Aspergillus. Based on these reference targets, the sequencing results targeting specific targets substantiate the efficacy of distinguishing the focal species from its closely related species. Notably, the amalgamation of room-temperature amplification and genome editing techniques demonstrates the capacity for rapid and accurate identification of genomic DNA samples at a concentration as low as 0.1 ng/μl within a concise 30-min timeframe. Importantly, this methodology circumvents the reliance on large specialized instrumentation by presenting a singular tube operational modality and allowing for visualized result assessment. These advancements aptly meet the exigencies of on-site detection requirements for the specified species, facilitating prompt diagnosis and food quality monitoring. Moreover, as an identification method based on species-specific genomic sequences, AGE shows promising potential as an effective tool for epidemiological research and species classification.

Green synthesis of bovine serum albumin–tailored silver nanoparticles from Aspergillus fumigatus: Statistical optimization, characterization, antioxidant, and cytotoxicity evaluation on colon cancer cells

Nanobiotechnology has evolved as a promising technology in developing therapeutically active materials. This study involved the biological synthesis of silver nanoparticles (AgNPs) from extracellular filtrate from the fungal species Aspergillus fumigatus to assess their antioxidant and cytotoxic activity under in‐vitro conditions. This method has become more reliable than physical and chemical approaches, attributed to its use of ecologically clean and non‐toxic methods. These synthesized nanoparticles are then characterized by UV–visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), dynamic light scattering, scanning electron microscope (SEM), differential scanning calorimetry, and X‐ray diffraction (XRD). Design optimization was done to optimize the selected variables to choose the best‐fit ratios for the experiment. UV spectroscopy showed the absorption peaks for AgNPs and bovine serum albumin (BSA) AgNPs at 300 and 315 nm. FTIR spectroscopy showed amide, carboxyl, and ester groups in BSA AgNPs, indicating their role in stabilizing nanoparticles. The particle size and zeta potential for AgNPs and BSA AgNPs were found to be 124.81 and 152.92 nm; zeta potentials for AgNPS and BSA AgNPs were found to be −13.3 and −15.6 mV. Various antioxidant studies like 2,2‐Diphenyl‐1‐picrylhydrazyl (DPPH), 2,2‐azinobis‐(3‐ethylbenzothiazoline‐6‐sulfonate) (ABTS), ion chelating assay, lipid peroxide assay, and malondialdehyde were carried out, indicating good antioxidant activity for synthesized nanoparticles. SEM images advocated good spherical images and are well dispersed. The cytotoxic assay performed on HT‐29 colon cancer cells exhibited good inhibition activity for AgNPs and BSA AgNPs, with an IC50 value of 120 and 100 μg/ml. These study results revealed that the synthesized AgNPs, on optimization through Box‐Behnken design, exhibited good antioxidant and cytotoxic activity.

Changes in the airway microbiome in patients with bronchiectasis.

This study used metagenomic next-generation sequencing (mNGS) technology to explore the changes of the microbial characteristics in the lower respiratory tract in patients with acute exacerbations of bronchiectasis (noncystic fibrosis) to guide clinical treatment and improve patients' quality of life and prognosis. This prospective study included 54 patients with acute exacerbation and 46 clinically stable patients admitted to the Respiratory and Critical Care Medicine Center of the People's Hospital of Xinjiang Uygur Autonomous Region from January 2020 to July 2022. Sputum was subjected to routine microbiological tests, and bronchoalveolar lavage fluid (BALF) samples were subjected to microbiological tests and mNGS of BALF before empirical antibiotic therapy. Serum inflammatory markers (white blood cell count, interleukin-6, procalcitonin, and C-reactive protein) were measured. In addition, we evaluated the pathogen of mNGS and compared the airway microbiome composition of patients with acute exacerbation and control patients. The mean age of our cohort was 56 ± 15.2 years. Eighty-nine patients had positive results by mNGS. There was a significant difference in the detection of viruses between the groups (χ2 = 6.954, P < .01). The fungal species Candida albicans, Pneumocystis jirovecii, and Aspergillus fumigatus were significantly more common in patients with acute exacerbations (χ2 = 5.98, P = .014). The bacterial species Acinetobacter baumannii, Mycobacterium tuberculosis, Haemophilus influenzae, Haemophilus parahaemolyticus, Abiotrophia defectiva, and Micromonas micros were significantly more prevalent in patients with acute exacerbations (χ2 = 4.065, P = .044). The most common bacterial species isolated from the sputum and BALF samples of patients with acute exacerbation was A. baumannii. Chlamydia psittaci was found in 4 patients. In addition, of 77 patients with negative sputum culture, 66 had positive results by mNGS, demonstrating the increased sensitivity and accuracy of mNGS. Patients with acute exacerbation of bronchiectasis tend to have mixed infections in the lower respiratory tract. The frequency of viruses, fungi, and Mycoplasma was higher in these patients. Our findings suggest that mNGS could be used to identify pathogenic microorganisms in these patients, increasing the effectiveness of antibiotic therapy.

Drug-Resistant Aspergillus spp.: A Literature Review of Its Resistance Mechanisms and Its Prevalence in Europe.

Infections due to the Aspergillus species constitute an important challenge for human health. Invasive aspergillosis represents a life-threatening disease, mostly in patients with immune defects. Drugs used for fungal infections comprise amphotericin B, triazoles, and echinocandins. However, in the last decade, an increased emergence of azole-resistant Aspergillus strains has been reported, principally belonging to Aspergillus fumigatus species. Therefore, both the early diagnosis of aspergillosis and its epidemiological surveillance are very important to establish the correct antifungal therapy and to ensure a successful patient outcome. In this paper, a literature review is performed to analyze the prevalence of Aspergillus antifungal resistance in European countries. Amphotericin B resistance is observed in 2.6% and 10.8% of Aspergillus fumigatus isolates in Denmark and Greece, respectively. A prevalence of 84% of amphotericin B-resistant Aspergillus flavus isolates is reported in France, followed by 49.4%, 35.1%, 21.7%, and 20% in Spain, Portugal, Greece, and amphotericin B resistance of Aspergillus niger isolates is observed in Greece and Belgium with a prevalence of 75% and 12.8%, respectively. The prevalence of triazole resistance of Aspergillus fumigatus isolates, the most studied mold obtained from the included studies, is 0.3% in Austria, 1% in Greece, 1.2% in Switzerland, 2.1% in France, 3.9% in Portugal, 4.9% in Italy, 5.3% in Germany, 6.1% in Denmark, 7.4% in Spain, 8.3% in Belgium, 11% in the Netherlands, and 13.2% in the United Kingdom. The mechanism of resistance is mainly driven by the TR34/L98H mutation. In Europe, no in vivo resistance is reported for echinocandins. Future studies are needed to implement the knowledge on the spread of drug-resistant Aspergillus spp. with the aim of defining optimal treatment strategies.

МИКОБИОТА В ДОННЫХ ГРУНТАХ ГОРЯЧИНСКОГО ТЕРМАЛЬНОГО ИСТОЧНИКА

The number of colony-forming units (CFU), composition and taxonomic structure of fungal biota in the bottom grounds of the Goryachinsk geothermal spring (Buryatia, Russian Federation) were determined by the cultural approach and the method of high-performance sequencing. The number of fungi in the grounds (0–3 cm) at the outlet of the spring and the watercourse at a short distance (3–100 m) varied in the range from several units to hundreds of CFU in 1 g. 70 isolates of fungi of 34 morphotypes were isolated by platings on nutrient media, of which 15 were identified to the species and 2 to the genus level. Its were thermophilic and thermotolerant species Aspergillus fumigatus, A. niger, A. nishimurae, A. terreus, Melanocarpus albomyces, Mycothermus thermophilus, Naganishia brisbanensis, Penicillium sp., Pseudothielavia terricola, Rhodotorula sp., Scedosporium apiospermum, Talaromyces flavus, Thermomyces dupontii, Thermothielavioides terrestris and Vishniacozyma carnescens. The method of high-performance sequencing of the ITS2 rDNA site in the source soils revealed an order of magnitude greater diversity of fungi, 149 species of 132 genera, and a total of 160 species were detected by both approaches. The number of identified operational-taxonomic units (OTE) to the species was 64.4%. In addition to ascomycetes and basidiomycetes, which were detected by platings on nutrient media, DNA barcoding showed the presence of representatives of the Phylums Mucoromycota, Mortierellomycota, Zoopagomycota, Chytridiomycota, Rozellomycota in the grounds. Moreover, among the fungi established by high-performance sequencing were not only thermotolerants, but also species with different resistance to high temperatures and trophic orientation. The application of both approaches provided more detailed information about the diversity of fungal organisms in the hot spring. However, in order to identify the inhabitant species of such ecotopes, a thorough analysis of their physiological and biochemical properties (which for many taxa is absent in due to volume) and the use of other approaches are necessary.

Presence of Aspergillus fumigatus with the TR34/L98H Cyp51A mutation and other azole-resistant aspergilli in the air of a zoological park

Antifungal-resistant fungi, including Aspergillus fumigatus and other Aspergillus species, pose an urgent threat to human and animal health. Furthermore, the environmental route of azole resistance selection due to the widespread use of azole fungicides in crop protection and other applications is a major public health issue. Although environmental surveillance of fungi is frequently performed in many zoological parks and wildlife rehabilitation centers, the antifungal susceptibility of recovered isolates is only rarely analyzed, which precludes a clear assessment of the threat posed by these fungi to captive animals. In this study, we assessed the presence of airborne azole-resistant Aspergillus spp., including the so-called ‘cryptic species’ (i.e., species which are phenotypically similar to more well-known aspergilli but clearly constitute different phylogenetic lineages) in a zoological park located in the city of Madrid, Spain. In general, our results revealed a low prevalence A. fumigatus and cryptic aspergilli with decreased susceptibility to azoles. However, we detected an A. fumigatus isolate with the TR34/L98H mutation in the gene encoding the lanosterol 14α-demethylase (Cyp51A), consisting of a tandem repeat of 34 base pairs in the promoter region and a lysine to histidine substitution at codon 98. Notably, this TR34/L98H mutation has been linked to the environmental route of azole resistance selection, thus highlighting the ‘One Health’ dimension of the emerging problem of antifungal resistance. In this context, continuous environmental surveillance of azole-resistant aspergilli in zoological parks and other similar animal facilities is recommended.

Prospection of Cellulolytic Fungi from Composted Samples of Saturated Horse Litter

The treatment of saturated horse beds before they arrive at their final destination is necessary to avoid the risk of animal and environmental contamination. For this purpose, the composting process has great functionality due its to low cost, effectiveness, and operational ease. However, because of the nature of the materials used, this process can be long, and it is necessary to improve it to optimize composting cycles. This work aimed to isolate and identify fungi present in the compost piles of saturated equine bedding made with shavings and rice straw, identifying those with the greatest potential for cellulase production. Using specific cellulolytic media containing shavings or rice straw, seven strains were isolated. The total cellulase enzymatic activity of the isolates from the beds made with shavings was lower than that obtained from rice straw beds. Four strains showed high enzymatic potential for use in the shavings substrate (MA -6 2 f1, MA -6 2 f2, MA -7 9, and MA -7 10) and three for the rice straw substrate (PA -7 5, PA -7 7, and PA -7 10). The isolate PA -7 5 reached 0.376 IU mL−1, the best index among all the isolates. These isolates were identified as belonging to the Aspergillus fumigatus species.

Multivariate analysis of enriched landfill soil consortia provide insight on the community structural perturbation and functioning during low-density polyethylene degradation

Plastic-enriched sites like landfills have immense potential for discovery of microbial consortia that can efficiently degrade plastics. In this study, we used a combination of culture enrichment, high-throughput PacBio sequencing of 16 S rRNA and the ITS gene, Fourier transform infrared (FTIR), and scanning electron microscopy (SEM) to examine the compositional and diversity perturbations of bacterial and fungal consortia from landfill soils and their impact on low-density polyethylene (LDPE) film biodegradation over a 90-day period. Results showed that enrichment cultures effectively utilized LDPE as a carbon source for cellular growth, resulting in significant weight reduction (22.4% and 55.6%) in the films. SEM analysis revealed marked changes in the micrometric surface characteristics (cracks, fissures, and erosion) and biofilm formation in LDPE films. FTIR analyses suggested structural and functional group modification related to C-H (2831–2943 cm⁻¹), and CH₂ (1400 cm⁻¹) stretching, CO and CC (680–950 cm⁻¹) scission, and CO incorporation (3320–3500 cm⁻¹) into the carbon backbone, indicative of LDPE polymer biodegradation. Enrichment cultures had lower diversity and richness of microbial taxa compared to soil samples, with LDPE as a carbon source having a direct influence on the structure and functioning of the microbial consortia. A total of 26 bacterial and 12 fungal OTU exhibiting high relative abundance and significant associations (IndVal > 0.7, q < 0.05) were identified in the enrichment culture. Bacterial taxa such as unclassified Parvibaculum FJ375498, Achromobacter xylosoxidans, unclassified Chitinophagaceae PAC002331, unclassified Paludisphaera and unclassified Comamonas JX898122, and six fungal species (Galactomyces candidus, Trichosporon chiropterorum, Aspergillus fumigatus, Penicillium chalabudae, Talaromyces thailandensis, and Penicillium citreosulfuratum) were identified as the putative LDPE degraders in the enrichment microbial consortium cultures. PICRUSt2 metagenomic functional profiling of taxonomic bacterial taxa abundances in both landfill soil and enrichment microbial consortia also revealed differential enrichment of energy production, stress tolerance, surface attachment and motility pathways, and xenobiotic degrading enzymes important for biofilm formation and hydrolytic/oxidative LDPE biodegradation. The findings shed light on the composition and structural changes in landfill soil microbial consortia during enrichment with LDPE as a carbon source and suggest novel LDPE-degrading bacterial and fungal taxa that could be explored for management of polyethylene pollution.

Background concentrations of airborne, culturable fungi and dust particles in urban, rural and mountain regions

Geographic location and meteorological factors can affect the content of bioaerosol concentrations. This study was conducted to determine the natural background concentrations of culturable fungal spores and dust particles in three different geographical areas. Focus was given to the dominant airborne genera Cladosporium, Penicillium, Aspergillus and the species Aspergillus fumigatus. The influence of weather conditions on the microorganism concentrations in urban, rural and mountain regions were examined. Possible correlations between particle counts and culturable fungal spore concentrations were investigated.125 measurements of the air were conducted using the air sampler MAS–100NT® and the particle counter Alphasense OPC–N3. The analyses of the collected samples were based on culture methods using different media.The highest median of fungal spore concentrations was detected in the urban region and was of 2.0 × 103 CFU/m3 for xerophilic fungi and 1.7 × 103 CFU/m3 for the genus Cladosporium. The concentrations of fine and coarse particles in rural and urban regions were the highest of 1.9 × 107 pa/m3 and 1.3 × 107 pa/m3, respectively. Little cloud cover and slight wind had a positive influence on the concentration of fungal spores. Furthermore, correlations were observed between air temperature and the concentrations of xerophilic fungi as well as the genera Cladosporium. In contrast, relative humidity correlated negatively with total fungi and Cladosporium and no correlation was found with the other fungi. For the region of Styria in summer and early autumn, the natural background concentration for xerophilic fungi ranged between 3.5 × 102 and 4.7 × 103 CFU/m3 air. No significant differences were detected between the fungal spore concentrations in urban, rural and mountainous regions.The data of this study could be used as a reference to compare the natural background concentrations of airborne culturable fungi in further studies concerning air quality assessment.

Phenotypic Array for Identification and Screening of Antifungals against Aspergillus Isolates from Respiratory Infections in KwaZulu Natal, South Africa.

The rapid emergence of invasive fungal infections correlates with the increasing population of immunocompromised individuals, with many cases leading to death. The progressive increase in the incidence of Aspergillus isolates is even more severe due to the clinical challenges in treating invasive infections in immunocompromised patients with respiratory conditions. Rapid detection and diagnosis are needed to reduce mortality in individuals with invasive aspergillosis-related infections and thus efficient identification impacts clinical success. The phenotypic array method was compared to conventional morphology and molecular identification on thirty-six Aspergillus species isolated from patients with respiratory infections at the Inkosi Albert Luthuli Hospital in Kwa-Zulu Natal. In addition, an antimicrobial array was also carried out to screen for possible novel antimicrobial compounds for treatment. Although traditional morphological techniques are useful, genetic identification was the most reliable, assigning 26 to Aspergillus fumigatus species, 8 Aspergillus niger, and 2 Aspergillus flavus including cryptic species of A. niger, A. tubingensis and A. welwitschiae. The phenotypic array technique was only able to identify isolates up to the genus level due to a lack of adequate reference clinical species in the database. However, this technique proved crucial in assessing a wide range of possible antimicrobial options after these isolates exhibited some resistance to azoles. Antifungal profiles of the thirty-six isolates on the routine azole voriconazole showed a resistance of 6%, with 61% having moderate susceptibility. All isolates resistant to the salvage therapy drug, posaconazole pose a serious concern. Significantly, A. niger was the only species resistant (25%) to voriconazole and has recently been reported as the species isolated from patients with COVID-19-associated pulmonary aspergillosis (CAPA). Phenotypic microarray showed that 83% of the isolates were susceptible to the 24 new compounds and novel compounds were identified for potentially effective combination treatment of fungal infections. This study also reports the first TR34/98 mutation in Aspergillus clinical isolates which is located in the cyp51A gene.

ORAL MANIFESTATIONS OF MYCOTIC INFECTIONS-A REVIEW

Fungal infections in humans occur as a result of defects in the immune system. The majority of opportunistic oral mucosal fungal infections are due to Candida albicans and Aspergillus fumigatus species. Mucor and Cryptococcus also have a major role in causing oral infections, whereas Geotrichum, Fusarium, Rhodotorula, Saccharomyces and Penicillium marneffei are uncommon pathogens in the oral cavity. . Oral candidiasis is generally a localized infection and rarely appears as a systemic fungal disease whereas oral non-Candidal fungal infections are usually signs of disseminated disease. Some of the non-Candidal fungi that were once considered exotic and geographically restricted are now seen worldwide. This review discusses various opportunistic fungal infections affecting the oral cavity including their morphology, clinical features and diagnostic methods

Bioluminescence Imaging, a Powerful Tool to Assess Fungal Burden in Live Mouse Models of Infection.

Aspergillus fumigatus and Cryptococcus neoformans species infections are two of the most common life-threatening fungal infections in the immunocompromised population. Acute invasive pulmonary aspergillosis (IPA) and meningeal cryptococcosis are the most severe forms affecting patients with elevated associated mortality rates despite current treatments. As many unanswered questions remain concerning these fungal infections, additional research is greatly needed not only in clinical scenarios but also under controlled preclinical experimental settings to increase our understanding concerning their virulence, host-pathogen interactions, infection development, and treatments. Preclinical animal models are powerful tools to gain more insight into some of these needs. However, assessment of disease severity and fungal burden in mouse models of infection are often limited to less sensitive, single-time, invasive, and variability-prone techniques such as colony-forming unit counting. These issues can be overcome by in vivo bioluminescence imaging (BLI). BLI is a noninvasive tool that provides longitudinal dynamic visual and quantitative information on the fungal burden from the onset of infection and potential dissemination to different organs throughout the development of disease in individual animals. Hereby, we describe an entire experimental pipeline from mouse infection to BLI acquisition and quantification, readily available to researchers to provide a noninvasive, longitudinal readout of fungal burden and dissemination throughout the course of infection development, which can be applied for preclinical studies into pathophysiology and treatment of IPA and cryptococcosis in vivo.

Synthesis, antimicrobial activities of metal (ii) complexes from salicylaldehyde and valine Schiff base

Complexes formed from the interaction of Fe(II), Co(II), Cu(II), and Zn(II) with Schiff base derived from salicylaldehyde and valine have been synthesized and characterized on the basis of melting point/decomposition temperature, solubility, molar conductance, UV spectroscopy and infrared spectral analysis. The Schiff base melted at a temperature of 208oC while the synthesized metal (II) complexes decomposed at a temperature range of 220-241°C. All the complexes were found to be soluble in water and DMSO but insoluble in acetonitrile, ether and hexane. Octahedral geometry around these metal ions has been proposed on the basis of magnetic and spectral studies. The synthesized Schiff base as well as the complexes were tested against the bacterial strains comprising Staphylococcus aureus (Gram positive), Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis and Klebsiella pneumonia (Gram negative) and two fungal species; Aspergillus fumigatus and mucor species. A comparative study of inhibition values of the Schiff base and its complexes indicated that the complexes exhibited higher antimicrobial activity than the free ligand.

Optimizing cultivation conditions for the highest expression of fungal allergens

BackgroundAny reliable allergy diagnosis depends on the quality of the testing material. In the case of fungal allergy, fungal extracts, typically used as test solutions, exhibit considerable differences in their allergenicity. Better knowledge of fungal allergen expression would enable the production of diagnostic fungal extracts of higher quality and, thus, improve the specificity and sensitivity of fungal allergy diagnosis. ObjectiveOur study aimed to find optimal cultivation conditions for the highest expression of fungal allergens. MethodsFungal species (Alternaria alternata, Ulocladium chartarum, Aspergillus fumigatus, Cladosporium herbarum, and Paecilomyces variotii) were cultivated under different conditions, and extracts were prepared from fungal material. To detect the expression of the homologous major allergens Alt a 1 and Ulo c 1 and of different fungal enolases, Western blots with allergen-specific antibodies were carried out. ResultsWestern blots performed with antibodies directed against Alt a 1 and enolases showed that the expression of fungal allergens is highly species-dependent. Even allergens of closely related fungal species and highly conserved, cross-reactive allergens display different expression patterns. ConclusionThis study exhibits the impact of different environmental conditions on the expression of the fungal allergens Alt a 1, Ulo c 1, and different fungal enolases. Furthermore, it broadens the knowledge regarding the expression pattern of the major fungal allergens Alt a 1 and Ulo c 1. Information obtained in this study will help to optimize fungal cultivation to produce diagnostic fungal extracts of high quality and, therefore, improve diagnostic specificity and sensitivity.

Dynamic full-field optical coherence tomography as complementary tool in fungal diagnostics

Histopathology and microscopic examination of infected tissue are the gold standards to prove the diagnosis of invasive fungal infection (IFI). Yet, they suffer from essential limitations that hamper rapid diagnosis and require the future development of new imaging tools dedicated to fungal diagnostics. To this end, the present work introduces the first use of dynamic full-field optical coherence tomography (D-FF-OCT) for the visualization of microscopic filamentous fungi. Data collected from the observation of three different fungal species (Nannizzia gypsea, Aspergillus fumigatus and Rhizopus arrhizus) confirm the ability of D-FF-OCT to visualize not only the main structures of all selected fungal species (hyphae, spores, conidia, sporulating structures), but also the metabolic activity of the organisms, which could provide additional help in the future to better characterize the signature of each fungal structure. These results demonstrate how D-FF-OCT could serve as potential complementary tool for rapid diagnosis of IFI in both intensive and non-intensive care units.

In Vitro Susceptibilities of Worldwide Isolates of Intrapulmonary Aspergillus Species and Important Candida Species in Sterile Body Sites against Important Antifungals: Data from the Antimicrobial Testing Leadership and Surveillance Program, 2017-2020.

To understand the changes of resistance in clinically commonly encountered fungi, we used the Antimicrobial Testing Leadership and Surveillance (ATLAS) database to explore in vitro antifungal susceptibilities against clinically important isolates of Aspergillus and Candida species (collected from intrapulmonary and sterile body areas, respectively). We applied the CLSI antifungal 2020 and the EUCAST antifungal 2020 guidelines. From 2017 to 2020, isolates of intrapulmonary Aspergillus fumigatus (n = 660), Aspergillus niger (n = 107), Aspergillus flavus (n = 96), Aspergillus terreus (n = 40), and Aspergillus nidulans species complex (n = 26) and sterile site-originated isolates of Candida albicans (n = 1,810), Candida glabrata (n = 894), Candida krusei (n = 120), Candida dubliniensis (n = 107), Candida lusitaniae (n = 82), Candida guilliermondii (n = 28), and Candida auris (n = 7) were enrolled in this study. Using the EUCAST 2020 breakpoints, it was demonstrated that amphotericin B and posaconazole displayed poor in vitro susceptibility rates against A. fumigatus isolates (<50% and 18.9%, respectively). In contrast, isavuconazole and itraconazole showed high in vitro potency against most Aspergillus isolates (>92%). Most intrapulmonary Aspergillus isolates exhibited MICs of ≤0.06 μg/mL to anidulafungin. Furthermore, intrapulmonary A. fumigatus isolates collected from Italy and the United Kingdom exhibited lower in vitro susceptibility to isavuconazole (72.2% and 69%, respectively) than those in the remaining ATLAS participant countries (>85%). Higher isavuconazole MIC90s against C. auris and C. guilliermondii (1 and 4 μg/mL, respectively) were observed compared to the other five Candida species. Despite the aforementioned MICs and susceptibilities against fungi, research needs to consider the pharmacokinetic (PK) profiles, pharmacodynamic (PD) parameters, and clinical treatment experience with antifungals against specific Aspergillus species. IMPORTANCE In addition to monitoring the antifungal susceptibilities of clinically important fungi, reviewing the PK/PD indices and the clinical therapy experience of antifungals under evaluation are important to guide an appropriate antifungal prescription. The efficacies of liposomal amphotericin B complex and anidulafungin for the treatment of pulmonary aspergillosis caused by different Aspergillus species need to be periodically evaluated in the future.

Emerging Fungal Infections: from the Fields to the Clinic, Resistant Aspergillus fumigatus and Dermatophyte Species: a One Health Perspective on an Urgent Public Health Problem.

Purpose of ReviewFor this review, we use a One Health approach to examine two globally emerging public health threats related to antifungal drug resistance: triazole-resistant Aspergillus fumigatus infections, which can cause a life-threatening illness in immunocompromised hosts, and antifungal-resistant dermatophytosis, which is an aggressive skin infection caused by dermatophyte molds. We describe the state of current scientific knowledge and outline necessary public health actions to address each issue.Recent FindingsRecent evidence has identified the agricultural use of triazole fungicides as an important driver of triazole-resistant A. fumigatus infections. Antifungal-resistant dermatophyte infections are likely driven by the inappropriate use of antifungal drugs and antibacterial and corticosteroid creams.SummaryThis review highlights the need for a One Health approach to address emerging antifungal resistant infections, emphasizing judicious antifungal use to preserve available treatments; strengthened laboratory capacity to identify antifungal resistance; and improved human, animal, and environmental surveillance to detect emerging resistance, monitor trends, and evaluate the effectiveness of efforts to decrease spread.