title: Identification of Microcystis aeruginosa Peptides Responsible for Allergic Sensitization and Characterization of Functional Interactions between Cyanobacterial Toxins and Immunogenic Peptides.
abstract: BACKGROUND
  The cyanobacterium species Microcystis aeruginosa produces microcystin and an array of diverse metabolites believed responsible for their toxicity and/or immunogenicity. Previously, chronic rhinitis patients were demonstrated to elicit a specific IgE response to nontoxic strains of M. aeruginosa by skin-prick testing, indicating that cyanobacteria allergenicity resides in a non-toxin-producing component of the organism.
  
  
  OBJECTIVE
  We sought to identify and characterize M. aeruginosa peptide(s) responsible for allergic sensitization in susceptible individuals, and we investigated the functional interactions between cyanobacterial toxins and their coexpressed immunogenic peptides.
  
  
  METHODS
  Sera from patients and extracts from M. aeruginosa toxic [MC(+)] and nontoxic [MC(-)] strains were used to test IgE-specific reactivity by direct and indirect ELISAs; 2D gel electrophoresis, followed by immunoblots and mass spectrometry (MS), was performed to identify the relevant sensitizing peptides. Cytotoxicity and mediator release assays were performed using the MC(+) and MC(-) lysates.
  
  
  RESULTS
  We found specific IgE to be increased more in response to the MC(-) strain than the MC(+) strain. This response was inhibited by preincubation of MC(-) lysate with increasing concentrations of microcystin. MS revealed that phycocyanin and the core-membrane linker peptide are the responsible allergens, and MC(-) extracts containing these proteins induced β-hexosaminidase release in rat basophil leukemia cells.
  
  
  CONCLUSIONS
  Phycobiliprotein complexes in M. aeruginosa have been identified as the relevant sensitizing proteins. Our finding that allergenicity is inhibited in a dose-dependent manner by microcystin toxin suggests that further investigation is warranted to understand the interplay between immunogenicity and toxicity of cyanobacteria under diverse environmental conditions.
  
  
  BACKGROUND
  Geh EN, Ghosh D, McKell M, de la Cruz AA, Stelma G, Bernstein JA. 2015. Identification of Microcystis aeruginosa peptides responsible for allergic sensitization and characterization of functional interactions between cyanobacterial toxins and immunogenic peptides. Environ Health Perspect 123:1159-1166; http://dx.doi.org/10.1289/ehp.1409065.
authors.affiliation: Allergy Section, Division of Immunology Allergy, and Rheumatology, Department of Internal Medicine, and.
authors.forename: Esmond N
authors.initials: EN
authors.lastname: Geh
authors.forename: Debajyoti
authors.initials: D
authors.lastname: Ghosh
authors.forename: Melanie
authors.initials: M
authors.lastname: McKell
authors.forename: Armah A
authors.initials: AA
authors.lastname: de la Cruz
authors.forename: Gerard
authors.initials: G
authors.lastname: Stelma
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
mesh_terms: D000485:Allergens / Q000032:analysis* / Q000276:immunology; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry; D001491:Basophils; D045744:Cell Line, Tumor; D000087522:Cyanobacteria Toxins; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D008387:Marine Toxins / Q000737:chemistry; D052998:Microcystins / Q000737:chemistry; D046931:Microcystis / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D010798:Phycocyanin / Q000276:immunology*; D051381:Rats; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D000485:Allergens; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D010455:Peptides; D010798:Phycocyanin; D007073:Immunoglobulin E; C078588:microcystin; D001619:beta-N-Acetylhexosaminidases