Polymorphism of Aspergillus Fumigatus Major Allergen Genes Associating with Their Isolated Sites Affects Their IgE Epitope Structures

2021 ◽  
Author(s):  
Rumi Konuma ◽  
Maiko Watanabe ◽  
Daisuke Irikura ◽  
Yoshiko Sugita-Konishi ◽  
Akiko Yamazaki ◽  
...  
Keyword(s):  
Amino Acid ◽  
Aspergillus Fumigatus ◽  
Amino Acid Substitution ◽  
Computer Software ◽  
Major Allergen ◽  
Nucleotide Mutation ◽  
Asp F 1 ◽  
Fungal Allergen ◽  
Structure Of Proteins ◽  
Ige Epitope

Abstract The circumstances in which organisms live induce polymorphism in their genes, including fungal allergen genes, leading to altered structures and functions of proteins, related to their pathogenicity. Major allergen genes of Aspergillus fumigatus, Asp f 1, Asp f 2, and Asp f 3, were examined in 59 strains [environment and animal/human-body origin] to determine their nucleotide sequences, and then categorized. The location and number of IgE epitopes on the allergen molecules were predicted using a computer software. The Asp f 1 gene was classified into two groups (f1-1 and f1-2). One of the groups possessed one-nucleotide mutation point with one amino-acid substitution. The mutated Asp f 2 gene accompanying 6-amino acid substitution was classified into 7 groups (f2-1 to f2-7). Six of the groups possessed a newborn IgE epitope. The Asp f 3 gene contained two mutations, resulted in three groups (f3-1 to f3-3) without any amino-acid substitutions. Category E, consisting of groups f1-1, f2-5, and f3-2, was specific to an environmental origin. Our findings suggest that nucleotide mutation of the fungal allergen genes, associated with the origin of the fungus, modifies the structure of proteins, and affects their pathogenic properties, such as the localization of IgE epitopes.

scholarly journals Diversity of TEM Mutants in Proteus mirabilis

1999 ◽  
Vol 43 (11) ◽  
pp. 2671-2677 ◽  
Author(s):  
R. Bonnet ◽  
C. De Champs ◽  
D. Sirot ◽  
C. Chanal ◽  
R. Labia ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Proteus Mirabilis ◽  
Clinical Isolates ◽  
Amino Acid Substitutions ◽  
First Report ◽  
Conjugative Plasmids ◽  
Extended Spectrum ◽  
Nucleotide Mutation

ABSTRACT In a survey of resistance to amoxicillin among clinical isolates ofProteus mirabilis, 10 TEM-type β-lactamases were characterized: (i) the well-known penicillinases TEM-1 and TEM-2, the extended-spectrum β-lactamases (ESBLs) TEM-3 and TEM-24, and the inhibitor-resistant TEM (IRT) TEM-44 and (ii) five novel enzymes, a penicillinase TEM-57 similar to TEM-1, an ESBL TEM-66 similar to TEM-3, and three IRTs, TEM-65, TEM-73, and TEM-74. The penicillinase TEM-57 and the ESBL TEM-66 differed from TEM-1 and TEM-3, respectively, by the amino acid substitution Gly-92→Asp (nucleotide mutation G-477→A). This substitution could have accounted for the decrease in pIs (5.2 for TEM-57 and 6.0 for TEM-66) but did not necessarily affect the intrinsic activities of these enzymes. The IRT TEM-65 was an IRT-1-like IRT (Cys-244) related to TEM-2 (Lys-39). The two other IRTs, TEM-73 and TEM-74, were related to IRT-1 (Cys-244) and IRT-2 (Ser-244), respectively, and harbored the amino acid substitutions Leu-21→Phe and Thr-265→Met. In this study, the ESBLs TEM-66, TEM-24, and TEM-3 were encoded by large (170- to 180-kb) conjugative plasmids that exhibited similar patterns after digestion and hybridization with the TEM and AAC(6′)I probes. The three IRTs TEM-65, TEM-73, and TEM-74 were encoded by plasmids that ranged in size from 42 to 70 kb but for which no transfer was obtained. The characterization of five new plasmid-mediated TEM-type β-lactamases and the first report of TEM-24 in P. mirabilis are evidence of the wide diversity of β-lactamases produced in this species and of its possible role as a β-lactamase-encoding plasmid reservoir.

scholarly journals Use of a Synthetic Peptide Epitope of Asp f 1, a Major Allergen or Antigen of Aspergillus fumigatus, for Improved Immunodiagnosis of Allergic Bronchopulmonary Aspergillosis

2004 ◽  
Vol 11 (3) ◽  
pp. 552-558 ◽  
Author(s):  
Taruna Madan ◽  
Priyanka Priyadarsiny ◽  
Mudit Vaid ◽  
Neel Kamal ◽  
Ashok Shah ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Synthetic Peptide ◽  
Immunoglobulin E ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Major Allergen ◽  
Specific Ige ◽  
Diagnostic Efficiency ◽  
Intradermal Testing ◽  
Peptide Epitope ◽  
Asp F 1

ABSTRACT Allergic bronchopulmonary aspergillosis (ABPA) is an immunologically complex allergic disorder caused by the fungal pathogen Aspergillus fumigatus. Elevated levels of total immunoglobulin E (IgE), specific IgE, and IgG antibodies in sera are important immunodiagnostic criteria for ABPA. International reference standards or standardized immunodiagnostic assays are not available due to a lack of well-defined diagnostic antigens. The present study was carried out to identify and evaluate the immunodiagnostic relevance of synthetic epitopic peptides of Asp f 1, a major allergen, antigen, or cytotoxin of A. fumigatus. Five overlapping peptides were synthesized from the N terminus of Asp f 1, one of the potential immunodominant regions predicted by algorithmic programs. The 11-amino-acid synthetic peptide (P1) significantly inhibited both IgG binding (89.10% ± 4.45%) and IgE binding (77.32% ± 3.38%) of the standardized diagnostic antigen (SDA) (a well-defined pool of diagnostically relevant allergens and antigens of A. fumigatus). With a panel of sera of ABPA patients, allergic patients with skin test negativity to A. fumigatus, and healthy individuals, P1 showed a higher diagnostic efficiency than SDA (specific IgG, 100%; specific IgE, 98.3%). The diagnostic efficiency of P1 could be attributed to the presence of homologous epitopes in various immunodominant allergens or antigens of A. fumigatus. The ability of P1 to induce histamine release from sensitized mast cells and a Th2 type of cytokine profile in peripheral blood mononuclear cells of ABPA patients suggests its potential for use in intradermal testing. P1 could be further explored for development of a standardized, specific, and sensitive immunodiagnostic test for aspergillosis.

scholarly journals Emergence of W272C Substitution in Hmg1 in a Triazole-Resistant Isolate of Aspergillus fumigatus from a Chinese Patient with Chronic Cavitary Pulmonary Aspergillosis

2021 ◽  
Author(s):  
Tianyu Liang ◽  
Xinyu Yang ◽  
Ruoyu Li ◽  
Ence Yang ◽  
Qiqi Wang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Aspergillus Fumigatus ◽  
Amino Acid Substitution ◽  
Coenzyme A ◽  
Chinese Patient ◽  
Resistant Isolate ◽  
Pulmonary Aspergillosis ◽  
First Case ◽  
Reductase Gene ◽  
Coa Reductase

Recently, mutations in the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase gene (hmg1) have been identified to be associated with triazole resistance in Aspergillus fumigatus. Here, we describe the first case of the G929C mutation in the hmg1 gene, leading to the W272C amino acid substitution, in a triazole-resistant isolate of A. fumigatus recovered from a chronic cavitary pulmonary aspergillosis patient who failed voriconazole therapy in China.

scholarly journals Vaccinations with Recombinant Variants of Aspergillus fumigatus Allergen Asp f 3 Protect Mice against Invasive Aspergillosis

2006 ◽  
Vol 74 (9) ◽  
pp. 5075-5084 ◽  
Author(s):  
James I. Ito ◽  
Joseph M. Lyons ◽  
Teresa B. Hong ◽  
Daniel Tamae ◽  
Yi-Kuang Liu ◽  
...  
Keyword(s):  
Invasive Aspergillosis ◽  
Aspergillus Fumigatus ◽  
Mononuclear Cells ◽  
Protein Vaccine ◽  
Novel Approach ◽  
In Vivo Testing ◽  
Asp F 1 ◽  
Fungal Allergen ◽  
Subcutaneous Immunization

ABSTRACT A vaccine that effectively protects immunocompromised patients against invasive aspergillosis is a novel approach to a universally fatal disease. Here we present a rationale for selection and in vivo testing of potential protein vaccine candidates, based on the modification of an immunodominant fungal allergen for which we demonstrate immunoprotective properties. Pulmonary exposure to viable Aspergillus fumigatus conidia as well as vaccination with crude hyphal extracts protects corticosteroid-immunosuppressed mice against invasive aspergillosis (J. I. Ito and J. M. Lyons, J. Infect. Dis. 186:869-871, 2002). Sera from the latter animals contain antibodies with numerous and diverse antigen specificities, whereas sera from conidium-exposed mice contain antibodies predominantly against allergen Asp f 3 (and some against Asp f 1), as identified by mass spectrometry. Subcutaneous immunization with recombinant Asp f 3 (rAsp f 3) but not with Asp f 1 was protective. The lungs of Asp f 3-vaccinated survivors were free of hyphae and showed only a patchy low-density infiltrate of mononuclear cells. In contrast, the nonimmunized animals died with invasive hyphal elements and a compact peribronchial infiltrate of predominately polymorphonuclear leukocytes. Three truncated versions of rAsp f 3, spanning amino acid residues 15 to 168 [rAsp f 3(15-168)], 1 to 142, and 15 to 142 and lacking the known bipartite sequence required for IgE binding, were also shown to be protective. Remarkably, vaccination with either rAsp f 3(1-142) or rAsp f 3(15-168) drastically diminished the production of antigen-specific antibodies compared to vaccination with the full-length rAsp f 3(1-168) or the double-truncated rAsp f 3(15-142) version. Our findings point to a possible mechanism in which Asp f 3 vaccination induces a cellular immune response that upon infection results in the activation of lymphocytes that in turn enhances and/or restores the function of corticosteroid-suppressed macrophages to clear fungal elements in the lungs.

scholarly journals Determination of Aspergillus Fumigatus Allergen 1 in Poultry Farms Using the Enzyme Immunoassay

2010 ◽  
Vol 61 (2) ◽  
pp. 167-173 ◽  
Author(s):  
Ljerka Prester ◽  
Jelena Macan ◽  
Kristina Matković ◽  
Marija Vučemilo
Keyword(s):  
Aspergillus Fumigatus ◽  
Enzyme Immunoassay ◽  
Limit Of Detection ◽  
Major Allergen ◽  
Indoor Dust ◽  
Enzyme Linked Immunosorbent Assay ◽  
Poultry Farms ◽  
Asp F 1 ◽  
Common Genus

Determination ofAspergillus FumigatusAllergen 1 in Poultry Farms Using the Enzyme ImmunoassayPoultry farms contain high levels of allergenic fungi, andAspergillusspp. is the most common genus of moulds.Aspergillus fumigatusantigens are responsible for the development of several respiratory diseases including asthma. The aim of this study was to measure the mass fraction of Asp f 1, a major allergen ofAsperillus fumigatusin 37 indoor dust samples collected from four poultry farms in a rural area of the Zagreb County (Croatia) using the enzyme-linked immunosorbent assay. More than 62 % of dust samples had detectable Asp f 1 levels (limit of detection 3.6 ng g-1). The overall mean Asp f 1 level was 17.9 ng g-1[range (3.8 to 72.4) ng g-1]. Satisfactory results were obtained for analytical within-run imprecision (6.7 %), between-run imprecision (10.5 %), and accuracy (91 % to 115 %). Microclimate parameters (air temperature, relative humidity, and velocity) were within the recommended ranges in all poultry farms. This study has shown that Asp f 1 settles on dust at poultry farms and that occupational exposure to this allergen deserves monitoring in livestock buildings.

scholarly journals Biochemical and structural characterization of quizalofop-resistant wheat acetyl-CoA carboxylase

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Raven Bough ◽  
Franck E. Dayan
Keyword(s):  
Amino Acid ◽  
Winter Wheat ◽  
Amino Acid Substitution ◽  
Reference Sequence ◽  
Cross Resistance ◽  
Homozygous Mutation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Nucleotide Mutation

AbstractA novel nucleotide mutation in ACC1 resulting in an alanine to valine amino acid substitution in acetyl-CoA carboxylase (ACCase) at position 2004 of the Alopecurus myosuroides reference sequence (A2004V) imparts quizalofop resistance in wheat. Genotypes endowed with the homozygous mutation in one or two ACC1 homoeologs are seven- and 68-fold more resistant to quizalofop than a wildtype winter wheat in greenhouse experiments, respectively. In vitro ACCase activities in soluble protein extracts from these varieties are 3.8- and 39.4-fold more resistant to quizalofop with the homozygous mutation in either one or two genomes, relative to the wildtype. The A2004V mutation does not alter the specific activity of wheat ACCase, suggesting that this resistance trait does not affect the catalytic functions of ACCase. Modeling of wildtype and quizalofop-resistant wheat ACCase demonstrates that the A2004V amino acid substitution causes a reduction in the volume of the binding pocket that hinders quizalofop’s interaction with ACCase. Docking studies confirm that the mutation reduces the binding affinity of quizalofop. Interestingly, the models suggest that the A2004V mutation does not affect haloxyfop binding. Follow up in vivo and in vitro experiments reveal that the mutation, in fact, imparts negative cross-resistance to haloxyfop, with quizalofop-resistant varieties exhibiting higher sensitivity to haloxyfop than the wildtype winter wheat line.

scholarly journals A thermodynamic model of protein structure evolution explains empirical amino acid rate matrices

2020 ◽  
Author(s):  
Christoffer Norn ◽  
Ingemar André ◽  
Douglas L. Theobald
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Evolutionary Dynamics ◽  
Fitness Function ◽  
Protein Structures ◽  
Evolutionary Model ◽  
Structure Evolution ◽  
Ancestral Sequences ◽  
Substitution Matrices ◽  
Nucleotide Mutation

AbstractProteins evolve under a myriad of biophysical selection pressures that collectively control the patterns of amino acid substitutions. Averaged over time and across proteins, these evolutionary pressures are sufficiently consistent to produce global substitution patterns that can be used to successfully find homologues, infer phylogenies, and reconstruct ancestral sequences. Although the factors which govern the variation of protein substitution rates has received much attention, the influence of thermodynamic stability constraints remains unresolved. Here we develop a simple model to calculate amino acid rate matrices from evolutionary dynamics controlled by a fitness function that reports on the thermodynamic effects of amino acid mutations in protein structures. This hybrid biophysical and evolutionary model accounts for nucleotide transition/transversion rate bias, multi-nucleotide codon changes, the number of codons per amino acid, and thermodynamic protein stability. We find that our theoretical model accurately recapitulates the complex pattern of empirical rates observed in common global amino acid substitution matrices used in phylogenetics. These results suggest that selection for thermodynamically stable proteins, coupled with nucleotide mutation bias filtered by the structure of the genetic code, is the primary global driver behind the amino acid substitution patterns observed in proteins throughout the tree of life.

scholarly journals Molecular allergen sensitization of Aspergillus fumigatus in allergic bronchopulmonary aspergillosis in Guangzhou, Southern China

2020 ◽  
Author(s):  
Wenting Luo ◽  
Haisheng Hu ◽  
Zehong Wu ◽  
Nili Wei ◽  
Huimin Huang ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Southern China ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Strongly Correlated ◽  
Guangzhou City ◽  
Allergen Components ◽  
Sige Level ◽  
Asthma Patients ◽  
Asp F 1 ◽  
Fungal Allergen

Abstract Background Few studies have assessed the sensitization of mycotic allergens and Aspergillus fumigatus molecular allergen. This study aimed to investigate the connection between A.fumigatus components and mycotic allergens between allergic bronchopulmonary aspergillosis (ABPA) patients and A. fumigatus (Af)-sensitized asthma. Methods Serum Penicillium chrysogenum , Cladosporium herbarum , Mucor racemosus , Candida albicans , Alternaria alternata , Helminthosporium halodes and A.fumigatus allergen components (Asp f 1, Asp f 2, Asp f 3, Asp f 4, and Asp f 6) sIgE level were measured via ImmunoCAP assay in 18 ABPA patients and 54 Af-sensitized asthma patients in Guangzhou city. Results 94.44% of ABPA patients and 87.04% of Af-sensitized asthma patients were co-sensitization to at least one another fungal allergen. The positivity rates of C. albicans ( P < 0.05) and A.alternata ( P < 0.05) were higher in ABPA than that in Af-sensitized asthma patients. The positive rates of Asp f 1 (88.89% vs 59.26%, P < 0.05), Asp f 2 (66.67% vs 33.33%, P < 0.05), Asp f 4 (61.11% vs 33.33%, P < 0.05), and Asp f 6 (66.67% vs 14.81%, P < 0.001) in ABPA were higher than those in Af-sensitized asthma patients. Patients with ABPA had higher IgE levels of Asp f 1 ( P < 0.05), Asp f 4 ( P < 0.05) and Asp f 6 ( P < 0.001) than those of Af-sensitized asthma patients. A.fumigatus was strongly correlated with C.herbarum ( r s = 0.688) in ABPA and A.alternata ( r s = 0.692) in Af-sensitized asthma patients. Optimal scale analysis was show that ABPA was more relevant to Af-components. (Cronbach`s alpha = 90.7%) Conclusion The A.fumigatus components and it`s connection with various mycotic allergens were different in ABPA and Af-sensitized asthma patients. This findings can expected to help local doctors in the diagnosis and immunotherapy of fungal allergies.

scholarly journals Biochemical and Structural Characterization of Quizalofop-Resistant Wheat Acetyl-Coa Carboxylase

2021 ◽  
Author(s):  
Raven Bough ◽  
Franck Dayan
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Specific Activity ◽  
Reference Sequence ◽  
Cross Resistance ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Nucleotide Mutation

Abstract A novel nucleotide mutation in ACC1 resulting in an alanine to valine amino acid substitution in acetyl-CoA carboxylase (ACCase) at position 2004 of the Alopecurus myosuroides reference sequence (A2004V) imparts quizalofop resistance in wheat. Genotypes endowed with one or two homozygous mutant ACC1 homoelogs are 7- and 68-fold more resistant to quizalofop than a wildtype variety in greenhouse experiments, respectively. In vitro assays of ACCase activities in protein extracts from these varieties reveal a 3.8- and 39.4-fold increase in resistance to quizalofop in the single and double-mutants relative to the wildtype. The A2004V mutation does not alter the specific activity of wheat ACCase, suggesting that ACCase mutants retain their normal catalytic functions. Modeling of wildtype and quizalofop-resistant wheat ACCase demonstrates that the A2004V amino acid substitution causes a reduction in the volume of the binding pocket that hinders quizalofop’s interaction with ACCase. Docking studies confirm that the mutation reduces the binding affinity of quizalofop. Interestingly, the models suggest that the A2004V mutation does not affect haloxyfop binding. Follow up in vivo and in vitro experiments reveal that the mutation, in fact, imparts negative cross-resistance to haloxyfop, with quizalofop-resistant varieties exhibiting more sensitivity to haloxyfop than the wildtype variety.

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