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Annual Review of Phytopathology 2011Aspergillus flavus is saprophytic soil fungus that infects and contaminates preharvest and postharvest seed crops with the carcinogenic secondary metabolite aflatoxin.... (Review)
Review
Aspergillus flavus is saprophytic soil fungus that infects and contaminates preharvest and postharvest seed crops with the carcinogenic secondary metabolite aflatoxin. The fungus is also an opportunistic animal and human pathogen causing aspergillosis diseases with incidence increasing in the immunocompromised population. Whole genome sequences of A. flavus have been released and reveal 55 secondary metabolite clusters that are regulated by different environmental regimes and the global secondary metabolite regulators LaeA and VeA. Characteristics of A. flavus associated with pathogenicity and niche specialization include secondary metabolite production, enzyme elaboration, and a sophisticated oxylipin host crosstalk associated with a quorum-like development program. One of the more promising strategies in field control involves the use of atoxic strains of A. flavus in competitive exclusion studies. In this review, we discuss A. flavus as an agricultural and medical threat and summarize recent research advances in genomics, elucidation of parameters of pathogenicity, and control measures.
Topics: Aflatoxins; Animals; Aspergillosis; Aspergillus flavus; Crops, Agricultural; Genes, Fungal; Genome, Fungal; Genomics; Humans; Multigene Family; Plant Diseases; Seeds; Virulence Factors
PubMed: 21513456
DOI: 10.1146/annurev-phyto-072910-095221 -
Microbiology (Reading, England) Jun 2007Aspergillus infections have grown in importance in the last years. However, most of the studies have focused on Aspergillus fumigatus, the most prevalent species in the... (Review)
Review
Aspergillus infections have grown in importance in the last years. However, most of the studies have focused on Aspergillus fumigatus, the most prevalent species in the genus. In certain locales and hospitals, Aspergillus flavus is more common in air than A. fumigatus, for unclear reasons. After A. fumigatus, A. flavus is the second leading cause of invasive aspergillosis and it is the most common cause of superficial infection. Experimental invasive infections in mice show A. flavus to be 100-fold more virulent than A. fumigatus in terms of inoculum required. Particularly common clinical syndromes associated with A. flavus include chronic granulomatous sinusitis, keratitis, cutaneous aspergillosis, wound infections and osteomyelitis following trauma and inoculation. Outbreaks associated with A. flavus appear to be associated with single or closely related strains, in contrast to those associated with A. fumigatus. In addition, A. flavus produces aflatoxins, the most toxic and potent hepatocarcinogenic natural compounds ever characterized. Accurate species identification within Aspergillus flavus complex remains difficult due to overlapping morphological and biochemical characteristics, and much taxonomic and population genetics work is necessary to better understand the species and related species. The flavus complex currently includes 23 species or varieties, including two sexual species, Petromyces alliaceus and P. albertensis. The genome of the highly related Aspergillus oryzae is completed and available; that of A. flavus in the final stages of annotation. Our understanding of A. flavus lags far behind that of A. fumigatus. Studies of the genomics, taxonomy, population genetics, pathogenicity, allergenicity and antifungal susceptibility of A. flavus are all required.
Topics: Allergens; Animals; Antigens, Fungal; Aspergillosis; Aspergillus flavus; Humans; Mycotoxins
PubMed: 17526826
DOI: 10.1099/mic.0.2007/007641-0 -
Mycoses May 2009Invasive aspergillosis is rare in immunocompetent people but contributes to significant morbidity and mortality in immunosuppressed patients. The majority (approximately... (Review)
Review
Invasive aspergillosis is rare in immunocompetent people but contributes to significant morbidity and mortality in immunosuppressed patients. The majority (approximately 80%) of invasive Aspergillus infections is caused by Aspergillus fumigatus. The second most frequent (approximately 15-20%) pathogenic species is Aspergillus flavus and to a lesser extent, Aspergillus niger and Aspergillus terreus. Aspergillus flavus has emerged as a predominant pathogen in patients with fungal sinusitis and fungal keratitis in several institutions worldwide. To date, there has not been any publication exclusively reviewing the topic of A. flavus in the literature. This article reviews the microbiology, toxigenicity and epidemiology of A. flavus as well as describes the clinical characteristics, diagnosis and management of infections caused by this organism.
Topics: Animals; Aspergillosis; Aspergillus flavus; Drug Resistance, Fungal; Humans; Mycotoxins; Virulence
PubMed: 19207851
DOI: 10.1111/j.1439-0507.2008.01642.x -
BMC Microbiology Nov 2021Penicillin was the first and most famous fungal secondary metabolite used as broad spectrum antibiotic that revolutionarised pharmaceutical research and also saved...
PROBLEM BACKGROUND
Penicillin was the first and most famous fungal secondary metabolite used as broad spectrum antibiotic that revolutionarised pharmaceutical research and also saved millions of lives. The over optimistic belief in 1967 that sufficient antibiotics had been discovered to defeat infectious diseases was quickly crashed with the appearance of multidrug resistant (MDR) bacteria in 1990s. This has posed a serious threat to mankind. Although scientists are making efforts to synthesize and discover new antibiotics there are not enough new drugs in pharmaceutical pipeline to beat the pace at which MDR bacteria are emerging. In view of this there is an urgent and serious medical need for new bioactive compounds to be discovered to treat infections caused by MDR pathogens. The present study is aimed to investigate the antibacterial potential of Aspergillus flavus originated compounds that may act as drug leads to treat future infections.
METHODOLOGY
Among the 6 isolated fungal strains from the rhizosphere of Mentha piperetta, one was processed for isolation of secondary metabolites on the basis of preliminary antibacterial testing. Observation of morphological and microscopic features helped in identification of the fungal strain as Aspergillus flavus. Potato Dextrose Agar (PDA) medium was used for fungal growth while Czapec Yeast Broth (CYB) medium was used for production of fungal metabolites. Column chromatography technique was utilized for purification of compound from crude fungal extract and the mass of the compound was determined using Liquid Chromatography Mass Spectrometry (LCMS) method. Structure elucidation of the pure compound was performed using 500 Varian Nuclear Magnetic Resonance (NMR) machine. Docking was performed using Glide SP algorithm. Agar well diffusion method was used to determine the invitro antibacterial potential of the compound against two MDR bacterial strains i.e. Staphylococcus aureus and Proteus vulgaris. For this a total of 4 dose concentrations i.e. (100, 250, 500, 1000 μg mL) of the compound were prepared and applied to bacterial strains on Mueller Hinton agar using tetracycline as control.
RESULTS
The chemical name of the purified compound from A. flavus was determined as (2E)-3-[(3S, 4R)-8-hydroxy-3, 4-dimethyl-1-oxo-3, 4-dihydro-1H-2- benzopyran-7-yl] prop-2-enoic acid with the formula CHO and exact mass of 262.08. The in-Silico analysis showed that this compound has the potential to inhibit the binding pocket of S. aureus TyrRS (1JII) with docking score of - 8.67 Kcal mole. The results obtained from invitro experiments were encouraging as at 1000 μg mL the compound showed 58.8% inhibition against S. aureus and 28% inhibition against P. vulgaris.
CONCLUSIONS
The pure compound with formula CHO and exact mass of 262 exhibited antibacterial potential both insilico and invitro against both Gram negative and Gram positive bacteria. The compound was more active against S. aureus in comparison to P. vulgaris. From the obtained results it is concluded that this compound can be used as potent antibacterial candidate but further studies will be needed prior to its use as antibiotic.
Topics: Anti-Bacterial Agents; Aspergillus flavus; Drug Resistance, Bacterial; Mentha piperita; Microbial Sensitivity Tests; Proteus vulgaris; Secondary Metabolism; Soil Microbiology; Staphylococcus aureus
PubMed: 34798838
DOI: 10.1186/s12866-021-02371-3 -
Applied Microbiology and Biotechnology Dec 2007Aspergillus flavus is a fungus that principally obtains resources for growth in a saprophytic mode. Yet, it also possesses the characteristics of an opportunistic... (Review)
Review
Aspergillus flavus is a fungus that principally obtains resources for growth in a saprophytic mode. Yet, it also possesses the characteristics of an opportunistic pathogen with a wide, non-specific host range (plants, animals, and insects). It has attained a high level of agricultural significance due to production of the carcinogen aflatoxin, which significantly reduces the value of contaminated crops. To access a large variety of nutrient substrates and penetrate host tissues, A. flavus possesses the capacity to produce numerous extracellular hydrolases. Most work on A. flavus hydrolases has focused on the serine and metalloproteinases, pectinase P2c, and amylase. Many hydrolases are presumed to function in polymer degradation and nutrient capture, but the regulation of hydrolase secretion is complex and substrate dependent. Proteinases are employed not only to help access protein substrates, such as elastin that is found in mammals and insects, but may also play roles in fungal defense and virulence. Secretion of the endopolygalacturonase P2c is strongly correlated with isolate virulence (against plants) and maceration of cotton boll tissues. In some hosts, secretion of alpha-amylase is critical for starch digestion and may play a critical role in induction of aflatoxin biosynthesis. Despite a significant body of work, much remains to be learned about hydrolase production and utilization by A. flavus. This information may be critical for the formulation of successful strategies to control aflatoxin contamination in affected commodities.
Topics: Aflatoxins; Amylases; Aspergillus flavus; Peptide Hydrolases; Polygalacturonase
PubMed: 17938911
DOI: 10.1007/s00253-007-1201-8 -
Comprehensive Reviews in Food Science... Nov 2020Filamentous fungi represent a rich source of extrolites, including secondary metabolites (SMs) comprising a great variety of astonishing structures and interesting... (Review)
Review
Filamentous fungi represent a rich source of extrolites, including secondary metabolites (SMs) comprising a great variety of astonishing structures and interesting bioactivities. State-of-the-art techniques in genome mining, genetic manipulation, and secondary metabolomics have enabled the scientific community to better elucidate and more deeply appreciate the genetic and biosynthetic chemical arsenal of these microorganisms. Aspergillus flavus is best known as a contaminant of food and feed commodities and a producer of the carcinogenic family of SMs, aflatoxins. This fungus produces many SMs including polyketides, ribosomal and nonribosomal peptides, terpenoids, and other hybrid molecules. This review will discuss the chemical diversity, biosynthetic pathways, and biological/ecological role of A. flavus SMs, as well as their significance concerning food safety and security.
Topics: Aflatoxins; Aspergillus flavus; Biosynthetic Pathways; Food Safety; Fungal Proteins; Genes, Fungal; Metabolome; Polyketides
PubMed: 33337039
DOI: 10.1111/1541-4337.12638 -
Yakugaku Zasshi : Journal of the... 2021The biological properties of elastase and Aspergillus flavus elastase inhibitor (AFLEI) from A. flavus were examined. Pathogenicity of elastase was investigated in mice... (Review)
Review
The biological properties of elastase and Aspergillus flavus elastase inhibitor (AFLEI) from A. flavus were examined. Pathogenicity of elastase was investigated in mice immunocompromised with cyclophosphamide, cyclosporine, prednisolone and carrageenan. Compared to cyclophosphamide immunocompromised mice treated with the spores of elastase nonproducing strain, cyclophosphamide immunocompromised mice treated with the spores of elastase producing strain had a significantly shorter survival rate. Molecular mass of AFLEI was determined to be 7525.8 Da. The elastolytic activity of elastases from A. flavus, and human leukocytes were inhibited by AFLEI. The primary structure of AFLEI was determined by the Edman sequencing procedure. The search for amino acid homology with other proteins demonstrated that amino acid residues 1 to 68 of AFLEI are 100% identical to residues 20 to 87 of the hypothetical protein AFUA_3G14940 of A. fumigatus. When immunocompromised mice administered of cyclophosphamide were infected by inhalation of A. flavus then administered amphotericin B (AMPH) alone or in combination with AFLEI, survival rate tended to be higher with combination treatment than with AMPH alone. Moreover, although extensive bleeding was seen in pathology sections taken from rat lung resected 24 h after elastase was administered to the lung via the bronchus, this bleeding was inhibited by AFLEI. The X-ray analysis has revealed that the structure of this inhibitor was wedge shaped and composed of a binding loop and a scaffold protein core. As synthetic-inhibitor strongly inhibited cytotoxicity induced by elastase in human-derived cells, it could prove beneficial for the treatment of pulmonary aspergillosis.
Topics: Amphotericin B; Animals; Aspergillus flavus; Disease Models, Animal; Enzyme Inhibitors; Hemorrhage; Humans; Immunocompromised Host; Lung Diseases; Mice; Pancreatic Elastase; Pulmonary Aspergillosis; Rats
PubMed: 33790120
DOI: 10.1248/yakushi.20-00193 -
Microbiology Spectrum Feb 2022Aspergillus flavus , a gene encoding a Zn(II)Cys DNA-binding domain, is an important transcriptional regulator of the aflatoxin biosynthesis gene cluster. Our previous...
Aspergillus flavus , a gene encoding a Zn(II)Cys DNA-binding domain, is an important transcriptional regulator of the aflatoxin biosynthesis gene cluster. Our previous results of Gene ontology (GO) analysis for the binding sites of AflR in A. flavus suggest that AflR may play an integrative regulatory role. In this study the Δ and overexpression (OE) strains based on the well-established double-crossover recombinational technique were constructed to investigate the integrative function of the gene in A. flavus. The disruption of severely affected the aflatoxin biosynthetic pathway, resulting in a significant decrease in aflatoxin production. The aflatoxin B (AFB) of the Δ strain was 180 ng/mL and aflatoxin B (AFB) was 2.95 ng/mL on YES medium for 5 days, which was 1/1,000 of that produced by the wild-type strain (WT). In addition, the Δ strain produced relatively sparse conidia and a very small number of sclerotia. On the seventh day, the sclerotia yield on each plate of the WT and OE strains exceeded 1,000, while the sclerotial formation of the Δ strain was not detected until 14 days. However, the biosynthesis of cyclopiazonic acid (CPA) was not affected by gene disruption. Transcriptomic analysis of the Δ strain grown on potato dextrose agar (PDA) plates at 0 h, 24 h, and 72 h showed that expression of clustering genes involved in the biosynthesis of aflatoxin was significantly downregulated. Meanwhile, the Δ strain compared with the WT strain showed significant expression differences in genes involved in spore germination, sclerotial development, and carbohydrate metabolism compared to the WT. The results demonstrated that the A. flavus gene also played a positive role in the fungal growth and development in addition to aflatoxin biosynthesis. Past studies of the A. flavus gene and its orthologues in related Aspergillus species were solely focused on their roles in secondary metabolism. In this study, we used the Δ and OE strains to demonstrate the role of in growth and development of A. flavus. For the first time, we confirmed that the Δ strain also was defective in production of conidia and sclerotia, asexual propagules of A. flavus. Our transcriptomic analysis further showed that genes involved in spore germination, sclerotial development, aflatoxin biosynssssthesis, and carbohydrate metabolism exhibited significant differences in the Δ strain compared with the WT strain. Our study indicates that AflR not only plays an important role in regulating aflatoxin synthesis but also in playing a positive role in the conidial formation and sclerotial development in A. flavus. This study reveals the critical and positive role of the gene in fungal growth and development, and provides a theoretical basis for the genetic studies of other .
Topics: Aflatoxins; Aspergillus flavus; Fungal Proteins; Gene Expression Profiling; Gene Expression Regulation, Fungal; Multigene Family; Phylogeny; Spores, Fungal; Transcription, Genetic
PubMed: 35080432
DOI: 10.1128/spectrum.00791-21 -
Medical Mycology 2009Most of the information available about Aspergillus infections has originated from the study of A. fumigatus, the most frequent species in the genus. This review aims to... (Comparative Study)
Comparative Study Review
Most of the information available about Aspergillus infections has originated from the study of A. fumigatus, the most frequent species in the genus. This review aims to compare the pathogenicity and clinical aspects of Aspergillosis caused by A. fumigatus an A. flavus. Experimental data suggests that A. flavus is more virulent than A. fumigatus. However, these were mostly models of disseminated Aspergillus infection which do not properly mimic the physiopathology of invasive aspergillosis, a condition that is usually acquired by inhalation. In addition, no conclusive virulence factor has been identified for Aspergillus species. A. flavus is a common cause of fungal sinusitis and cutaneous infections. Chronic conditions such as chronic cavitary pulmonary aspergillosis and sinuses fungal balls have rarely been associated with A. flavus. The bigger size of A. flavus spores, in comparison to those of A. fumigatus spores, may favour their deposit in the upper respiratory tract. Differences between these species justify the need for a better understanding of A. flavus infections.
Topics: Animals; Aspergillosis; Aspergillus flavus; Aspergillus fumigatus; Humans
PubMed: 18654921
DOI: 10.1080/13693780802247702 -
Acta Microbiologica Et Immunologica... Dec 2016Due to the climate change, aflatoxigenic Aspergillus species and strains have appeared in several European countries, contaminating different agricultural commodities...
Due to the climate change, aflatoxigenic Aspergillus species and strains have appeared in several European countries, contaminating different agricultural commodities with aflatoxin. Our aim was to screen the presence of aflatoxigenic fungi in maize fields throughout the seven geographic regions of Hungary. Fungi belonging to Aspergillus section Flavi were isolated in the ratio of 26.9% and 42.3% from soil and maize samples in 2013, and these ratios decreased to 16.1% and 34.7% in 2014. Based on morphological characteristics and the sequence analysis of the partial calmodulin gene, all isolates proved to be Aspergillus flavus, except four strains, which were identified as Aspergillus parasiticus. About half of the A. flavus strains and all the A. parasiticus strains were able to synthesize aflatoxins. Aflatoxigenic Aspergillus strains were isolated from all the seven regions of Hungary. A. parasiticus strains were found in the soil of the regions Southern Great Plain and Southern Transdanubia and in a maize sample of the region Western Transdanubia. In spite of the fact that aflatoxins have rarely been detected in feeds and foods in Hungary, aflatoxigenic A. flavus and A. parasiticus strains are present in the maize culture throughout Hungary posing a potential threat to food safety.
Topics: Aflatoxins; Aspergillus; Aspergillus flavus; Hungary; Plant Diseases; Soil Microbiology; Zea mays
PubMed: 27842453
DOI: 10.1556/030.63.2016.012