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MBio Dec 2022Aspergillus fumigatus is a human fungal pathogen that is most often avirulent in immunecompetent individuals because the innate immune system is efficient at eliminating...
Aspergillus fumigatus is a human fungal pathogen that is most often avirulent in immunecompetent individuals because the innate immune system is efficient at eliminating fungal conidia. However, recent clinical observations have shown that severe influenza A virus (IAV) infection can lead to secondary A. fumigatus infections with high mortality. Little is currently known about how IAV infection alters the innate antifungal immune response. Here, we established a murine model of IAV-induced A. fumigatus (IAV-) superinfection by inoculating mice with IAV followed 6 days later by A. fumigatus conidia challenge. We observed increased mortality in the IAV--superinfected mice compared to mice challenged with either IAV or A. fumigatus alone. A. fumigatus conidia were able to germinate and establish a biofilm in the lungs of the IAV- superinfection group, which was not seen following fungal challenge alone. While we did not observe any differences in inflammatory cell recruitment in the IAV- superinfection group compared to single-infection controls, we observed defects in Aspergillus conidial uptake and killing by both neutrophils and monocytes after IAV infection. pHrodo Green zymosan bioparticle (pHrodo-zymosan) and CM-H2DCFDA [5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate] staining, indicators of phagolysosome maturation and reactive oxygen species (ROS) production, respectively, revealed that the fungal killing defect was due in part to reduced phagolysosome maturation. Collectively, our data demonstrate that the ability of neutrophils and monocytes to kill and clear Aspergillus conidia is strongly reduced in the pulmonary environment of an IAV-infected lung, which leads to invasive pulmonary aspergillosis and increased overall mortality in our mouse model, recapitulating what is observed clinically in humans. Influenza A virus (IAV) is a common respiratory virus that causes seasonal illness in humans, but can cause pandemics and severe infection in certain patients. Since the emergence of the 2009 H1N1 pandemic strains, there has been an increase in clinical reports of IAV-infected patients in the intensive care unit (ICU) developing secondary pulmonary aspergillosis. These cases of flu-Aspergillus superinfections are associated with worse clinical outcomes than secondary bacterial infections in the setting of IAV. To date, we have a limited understanding of the cause(s) of secondary fungal infections in immunocompetent hosts. IAV-induced modulation of cytokine production and innate immune cellular function generates a unique immune environment in the lung, which could make the host vulnerable to a secondary fungal infection. Our work shows that defects in phagolysosome maturation in neutrophils and monocytes after IAV infection impair the ability of these cells to kill A. fumigatus, thus leading to increased fungal germination and growth and subsequent invasive aspergillosis. Our work lays a foundation for future mechanistic studies examining the exact immune modulatory events occurring in the respiratory tract after viral infection leading to secondary fungal infections.
Topics: Humans; Animals; Mice; Aspergillus fumigatus; Spores, Fungal; Superinfection; Influenza A Virus, H1N1 Subtype; Zymosan; Aspergillosis; Aspergillus
PubMed: 36377895
DOI: 10.1128/mbio.02854-22 -
Molecules (Basel, Switzerland) Nov 2023Alkaloids represent a large family of natural products with diverse structures and bioactivities. These compounds and their derivatives have been widely used in clinics... (Review)
Review
Alkaloids represent a large family of natural products with diverse structures and bioactivities. These compounds and their derivatives have been widely used in clinics to treat various diseases. The endophytic is a filamentous fungus renowned for its extraordinary ability to produce active natural products of high therapeutic value and economic importance. This review is the first to focus on -derived alkaloids. Through an extensive literature review and data analysis, 263 alkaloids are categorized according to their structural features into those containing cytochalasans, diketopiperazine alkaloids, quinazoline alkaloids, quinoline alkaloids, indole alkaloids, pyrrolidine alkaloids, and others. These metabolites exhibited diverse biological activities, such as antibacterial activity, cytotoxicity, anti-inflammatory activity, and α-glucosidase, ACE, and DPPH inhibitory activities. The bioactivity, structural diversity, and occurrence of these alkaloids are reviewed in detail.
Topics: Alkaloids; Aspergillus; Fungi; Indole Alkaloids; Plants; Biological Products
PubMed: 38067519
DOI: 10.3390/molecules28237789 -
PloS One 2022The higher airborne microbial concentration in indoor areas might be responsible for the adverse indoor air quality, which relates well with poor respiratory and general...
The higher airborne microbial concentration in indoor areas might be responsible for the adverse indoor air quality, which relates well with poor respiratory and general health effects in the form of Sick building syndromes. The current study aimed to isolate and characterize the seasonal (winter and spring) levels of culturable bio-aerosols from indoor air, implicating human health by using an epidemiological health survey. Microorganisms were identified by standard macro and microbiological methods, followed by biochemical testing and molecular techniques. Sampling results revealed the bacterial and fungal aerosol concentrations ranging between (300-3650 CFU/m3) and (300-4150 CFU/m3) respectively, in different microenvironments during the winter season (December-February). However, in spring (March-May), bacterial and fungal aerosol concentrations were monitored, ranging between (450-5150 CFU/m3) and (350-5070 CFU/m3) respectively. Interestingly, Aspergillus and Cladosporium were the majorly recorded fungi whereas, Staphylococcus, Streptobacillus, and Micrococcus found predominant bacterial genera among all the sites. Taken together, the elevated levels of bioaerosols are the foremost risk factor that can lead to various respiratory and general health issues in additional analysis, the questionnaire survey indicated the headache (28%) and allergy (20%) were significant indoor health concerns. This type of approach will serve as a foundation for assisting residents in taking preventative measures to avoid exposure to dangerous bioaerosols.
Topics: Air Microbiology; Air Pollution, Indoor; Aspergillus; Bacteria; Cladosporium; Environmental Monitoring; Humans; Seasons; Sick Building Syndrome
PubMed: 35213573
DOI: 10.1371/journal.pone.0264226 -
Frontiers in Immunology 2023The opportunistic filamentous fungus causes invasive pulmonary aspergillosis (IPA) that often turns into a fatal infection in immunocompromised hosts. However, the...
INTRODUCTION
The opportunistic filamentous fungus causes invasive pulmonary aspergillosis (IPA) that often turns into a fatal infection in immunocompromised hosts. However, the virulence capacity of different species and host inflammation induced by different species in IPA are not well understood.
METHODS
In the present study, host inflammation, antimicrobial susceptibilities and virulence were compared among clinical strains isolated from IPA patients.
RESULTS
A total of 46 strains were isolated from 45 patients with the invasive infection, of which 35 patients were diagnosed as IPA. was the dominant etiological agent appearing in 25 cases (54.3%). We found that the CRP level and leukocyte counts (elevated neutrophilic granulocytes and monocytes, and reduced lymphocytes) were significantly different in IPA patients when compared with healthy individuals ( < 0.05). Antifungal susceptibilities of these Aspergillus isolates from IPA showed that 91%, 31%, 14%, and 14% were resistant to Fluconazole, Micafungin, Amphotericin B and Terbinafine, respectively. The survival rate of larvae infected by was lower than larvae infected by or ( < 0.05).
DISCUSSION
was the dominant clinical etiological agent. Given the prevalence of in our local clinical settings, we may face greater challenges when treating IPA patients.
Topics: Humans; Invasive Pulmonary Aspergillosis; Virulence; Aspergillus; Antifungal Agents; Aspergillus flavus; Inflammation
PubMed: 37063826
DOI: 10.3389/fimmu.2023.1155184 -
Molecules (Basel, Switzerland) Apr 2023The genus, the etiological agent of aspergillosis, is an important food contaminant and mycotoxin producer. Plant extracts and essential oils are a source of bioactive...
The genus, the etiological agent of aspergillosis, is an important food contaminant and mycotoxin producer. Plant extracts and essential oils are a source of bioactive substances with antimicrobial potential that can be used instead of synthetic food preservatives. Species from the Lauraceae family and the genus have been used as traditional medicinal herbs. Their essential oils can be nanoemulsified to enhance their stability and bioavailability and increase their use. Therefore, this study sought to prepare and characterize both nanoemulsion and essential oil from the 's leaves, a native and endemic species from the Mata Atlântica forest in Brazil, and evaluate the activity against RC 2054, NRRL 2999, and NRRL 3174. The products were added to Sabouraud Dextrose Agar at concentrations of 256, 512, 1024, 2048, and 4096 µg/mL. The strains were inoculated and incubated for up to 96 h with two daily measurements. The results did not show fungicidal activity under these conditions. A fungistatic effect, however, was observed. The nanoemulsion decreased the fungistatic concentration of the essential oil more than ten times, mainly in . There were no significant changes in aflatoxin production.
Topics: Oils, Volatile; Ocotea; Aspergillus; Aspergillus flavus; Aflatoxins
PubMed: 37110671
DOI: 10.3390/molecules28083437 -
Current Protocols Dec 2021The larval zebrafish is an increasingly popular host model for the study of Aspergillosis. The visual accessibility, genetic resources, small size, and ease of handling...
The larval zebrafish is an increasingly popular host model for the study of Aspergillosis. The visual accessibility, genetic resources, small size, and ease of handling make zebrafish larvae compatible with higher-throughput investigation of fungal virulence and host resistance mechanisms. This article provides the protocols needed to prepare Aspergillus fumigatus spore inocula and use microinjection to infect the hindbrain ventricle of zebrafish larvae. Furthermore, we include protocols for analyzing host survival, immobilizing larvae for live imaging, and suggestions for image analysis. © 2021 Wiley Periodicals LLC. Support Protocol 1: Preparing Aspergillus spores Support Protocol 2: Dechorionating zebrafish embryos Support Protocol 3: Generating transparent larvae with 1-phenyl 2-thiourea (PTU) Basic Protocol 1: Hindbrain microinjection of zebrafish larvae with Aspergillus spores Basic Protocol 2: Survival analysis Basic Protocol 3: Multi-day imaging of infected larvae Alternate Protocol: Embedding larvae in low-melting-point agarose.
Topics: Animals; Aspergillosis; Aspergillus fumigatus; Larva; Virulence; Zebrafish
PubMed: 34875146
DOI: 10.1002/cpz1.317 -
Molecules (Basel, Switzerland) Dec 2019Microbial transformation of licochalcones B (), C (), D (), and H () using the filamentous fungi and was investigated. Fungal transformation of the licochalcones...
Microbial transformation of licochalcones B (), C (), D (), and H () using the filamentous fungi and was investigated. Fungal transformation of the licochalcones followed by chromatographic separations led to the isolation of ten new compounds -, including one hydrogenated, three dihydroxylated, three expoxidized, and three glucosylated metabolites. Their structures were elucidated by combined analyses of UV, IR, MS, NMR, and CD spectroscopic data. Absolute configurations of the 2″,3″-diols in the three dihydroxylated metabolites were determined by ECD experiments according to the Snatzke's method. The - isomerization was observed for the metabolites , , , and as evidenced by the analysis of their H-NMR spectra and HPLC chromatograms. This could be useful in better understanding of the - isomerization mechanism of retrochalcones. The fungal transformation described herein also provides an effective method to expand the structural diversity of retrochalcones for further biological studies.
Topics: Aspergillus niger; Biodegradation, Environmental; Chalcones; Chromatography, High Pressure Liquid; Fungi; Magnetic Resonance Spectroscopy; Molecular Structure; Transformation, Bacterial
PubMed: 31878031
DOI: 10.3390/molecules25010060 -
Toxins Nov 2021Aflatoxin is a carcinogenic mycotoxin produced by . Non-aflatoxigenic (Non-tox) isolates are deployed in corn fields as biocontrol because they substantially reduce...
Aflatoxin is a carcinogenic mycotoxin produced by . Non-aflatoxigenic (Non-tox) isolates are deployed in corn fields as biocontrol because they substantially reduce aflatoxin contamination via direct replacement and additionally via direct contact or touch with toxigenic (Tox) isolates and secretion of inhibitory/degradative chemicals. To understand touch inhibition, HPLC analysis and RNA sequencing examined aflatoxin production and gene expression of Non-tox isolate 17 and Tox isolate 53 mono-cultures and during their interaction in co-culture. Aflatoxin production was reduced by 99.7% in 72 h co-cultures. Fewer than expected unique reads were assigned to Tox 53 during co-culture, indicating its growth and/or gene expression was inhibited in response to Non-tox 17. Predicted secreted proteins and genes involved in oxidation/reduction were enriched in Non-tox 17 and co-cultures compared to Tox 53. Five secondary metabolite (SM) gene clusters and kojic acid synthesis genes were upregulated in Non-tox 17 compared to Tox 53 and a few were further upregulated in co-cultures in response to touch. These results suggest Non-tox strains can inhibit growth and aflatoxin gene cluster expression in Tox strains through touch. Additionally, upregulation of other SM genes and redox genes during the biocontrol interaction demonstrates a potential role of inhibitory SMs and antioxidants as additional biocontrol mechanisms and deserves further exploration to improve biocontrol formulations.
Topics: Aflatoxins; Aspergillus flavus; Coculture Techniques; Genes, Fungal; Multigene Family
PubMed: 34822579
DOI: 10.3390/toxins13110794 -
Journal of Hazardous Materials Sep 2022The performance of Aspergillus niger pellets to remove selenite and tellurite from wastewater using batch and continuous fungal pelleted bioreactors was investigated....
The performance of Aspergillus niger pellets to remove selenite and tellurite from wastewater using batch and continuous fungal pelleted bioreactors was investigated. The acid hydrolysate of brewer's spent grain (BSG) was utilized by A. niger as the electron donor for selenite and tellurite reduction. The dilution of BSG hydrolysate using mineral medium had a positive effect on the selenite and tellurite removal efficiency with a 1:3 ratio giving the best efficiency. However, selenite and tellurite inhibited fungal growth with a 40.9% and 27.3% decrease in the A. niger biomass yield in the presence of 50 mg/L selenite and tellurite, respectively. The maximum selenite and tellurite removal efficiency using 25% BSG hydrolysate in batch incubations amounted to 72.8% and 99.5% Two fungal pelleted bioreactors were operated in continuous mode using BSG hydrolysate as the substrate. Both the selenite and tellurite removal efficiencies during steady state operation were > 80% with tellurite showing a maximum removal efficiency of 98.5% at 10 mg/L influent concentration. Elemental Se nanospheres for selenite and both Te nanospheres and nanorods for tellurite were formed within the fungal pellets. This study demonstrates the suitability BSG hydrolysate as a low cost carbon source for removal of selenite and tellurite using fungal pellet bioreactors.
Topics: Aspergillus niger; Lignin; Selenious Acid; Tellurium
PubMed: 35728327
DOI: 10.1016/j.jhazmat.2022.129333 -
Applied and Environmental Microbiology Nov 2021Ergot alkaloids derived from lysergic acid have impacted humanity as contaminants of crops and as the bases of pharmaceuticals prescribed to treat dementia, migraines,...
Ergot alkaloids derived from lysergic acid have impacted humanity as contaminants of crops and as the bases of pharmaceuticals prescribed to treat dementia, migraines, and other disorders. Several plant-associated fungi in the Clavicipitaceae produce lysergic acid derivatives, but many of these fungi are difficult to culture and manipulate. Some Aspergillus species, which may be more ideal experimental and industrial organisms, contain an alternate branch of the ergot alkaloid pathway, but none were known to produce lysergic acid derivatives. We mined the genomes of Aspergillus species for ergot alkaloid synthesis () gene clusters and discovered that three species, A. leporis, A. homomorphus, and A. hancockii, had clusters indicative of the capacity to produce a lysergic acid amide. In culture, , , and produced lysergic acid amides, predominantly lysergic acid α-hydroxyethylamide (LAH). Aspergillus leporis and produced high concentrations of LAH and secreted most of their ergot alkaloid yield into the culture medium. Phylogenetic analyses indicated that genes encoding enzymes leading to the synthesis of lysergic acid were orthologous to those of the lysergic acid amide-producing Clavicipitaceae; however, genes to incorporate lysergic acid into an amide derivative evolved from different ancestral genes in the Aspergillus species. Our data demonstrate that fungi outside the Clavicipitaceae produce lysergic acid amides and indicate that the capacity to produce lysergic acid evolved once, but the ability to insert it into LAH evolved independently in Aspergillus species and the Clavicipitaceae. The LAH-producing Aspergillus species may be useful for the study and production of these pharmaceutically important compounds. Lysergic acid derivatives are specialized metabolites with historical, agricultural, and medical significance and were known heretofore only from fungi in one family, the Clavicipitaceae. Our data show that several Aspergillus species, representing a different family of fungi, also produce lysergic acid derivatives and that the ability to put lysergic acid into its amide forms evolved independently in the two lineages of fungi. From microbiological and pharmaceutical perspectives, the Aspergillus species may represent better experimental and industrial organisms than the currently employed lysergic acid producers of the plant-associated Clavicipitaceae. The observation that both lineages independently evolved the derivative lysergic acid α-hydroxyethylamide (LAH), among many possible lysergic acid amides, suggests selection for this metabolite.
Topics: Amides; Aspergillus; Biological Evolution; Hypocreales; Lysergic Acid; Lysergic Acid Diethylamide; Phylogeny
PubMed: 34586904
DOI: 10.1128/AEM.01801-21