title: Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens.
abstract: BACKGROUND
  Sporothrix schenckii and associated species are agents of human and animal sporotrichosis that cause large sapronoses and zoonoses worldwide. Epidemiological surveillance has highlighted an overwhelming occurrence of the highly pathogenic fungus Sporothrix brasiliensis during feline outbreaks, leading to massive transmissions to humans. Early diagnosis of feline sporotrichosis by demonstrating the presence of a surrogate marker of infection can have a key role for selecting appropriate disease control measures and minimizing zoonotic transmission to humans.
  
  
  METHODS
  We explored the presence and diversity of serum antibodies (IgG) specific against Sporothrix antigens in cats with sporotrichosis and evaluated the utility of these antibodies for serodiagnosis. Antigen profiling included protein extracts from the closest known relatives S. brasiliensis and S. schenckii. Enzyme-linked immunosorbent assays and immunoblotting enabled us to characterize the major antigens of feline sporotrichosis from sera from cats with sporotrichosis (n = 49), healthy cats (n = 19), and cats with other diseases (n = 20).
  
  
  RESULTS
  Enzyme-linked immunosorbent assay-based quantitation of anti-Sporothrix IgG exhibited high sensitivity and specificity in cats with sporotrichosis (area under the curve, 1.0; 95% confidence interval, 0.94-1; P<0.0001) versus controls. The two sets of Sporothrix antigens were remarkably cross-reactive, supporting the hypothesis that antigenic epitopes may be conserved among closely related agents. One-dimensional immunoblotting indicated that 3-carboxymuconate cyclase (a 60-kDa protein in S. brasiliensis and a 70-kDa protein in S. schenckii) is the immunodominant antigen in feline sporotrichosis. Two-dimensional immunoblotting revealed six IgG-reactive isoforms of gp60 in the S. brasiliensis proteome, similar to the humoral response found in human sporotrichosis.
  
  
  CONCLUSIONS
  A convergent IgG-response in various hosts (mice, cats, and humans) has important implications for our understanding of the coevolution of Sporothrix and its warm-blooded hosts. We propose that 3-carboxymuconate cyclase has potential for the serological diagnosis of sporotrichosis and as target for the development of an effective multi-species vaccine against sporotrichosis in animals and humans.
authors: Department of Microbiology, Immunology and Parasitology, Discipline of Cellular Biology, Federal University of São Paulo, São Paulo, Brazil.
authors: Anderson Messias
authors: AM
authors: Rodrigues
authors: Department of Microbiology, Immunology and Parasitology, Discipline of Cellular Biology, Federal University of São Paulo, São Paulo, Brazil.
authors: Geisa Ferreira
authors: GF
authors: Fernandes
authors: Department of Microbiology, Immunology and Parasitology, Discipline of Cellular Biology, Federal University of São Paulo, São Paulo, Brazil.
authors: Leticia Mendes
authors: LM
authors: Araujo
authors: Department of Microbiology, Immunology and Parasitology, Discipline of Cellular Biology, Federal University of São Paulo, São Paulo, Brazil.
authors: Paula Portella
authors: PP
authors: Della Terra
authors: Department of Microbiology, Immunology and Parasitology, Discipline of Cellular Biology, Federal University of São Paulo, São Paulo, Brazil.
authors: Priscila Oliveira
authors: PO
authors: dos Santos
authors: Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (INI/Fiocruz), Rio de Janeiro, Brazil.
authors: Sandro Antonio
authors: SA
authors: Pereira
authors: Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (INI/Fiocruz), Rio de Janeiro, Brazil.
authors: Tânia Maria Pacheco
authors: TM
authors: Schubach
authors: Department of Microbiology and Immunology, Biomedical Sciences Institute, Federal University of Alfenas, Alfenas, Brazil.
authors: Eva
authors: E
authors: Burger
authors: Instituto de Biologia (IBRAG), Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Leila Maria
authors: LM
authors: Lopes-Bezerra
authors: Department of Microbiology, Immunology and Parasitology, Discipline of Cellular Biology, Federal University of São Paulo, São Paulo, Brazil.
authors: Zoilo Pires
authors: ZP
authors: de Camargo
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood / Q000276:immunology*; D000946:Antigens, Fungal / Q000032:analysis / Q000276:immunology; D002371:Cat Diseases / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology; D002415:Cats; D003429:Cross Reactions; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D056724:Immunity, Humoral; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D040901:Proteomics; D012698:Serologic Tests; D013175:Sporothrix / Q000737:chemistry / Q000276:immunology*; D013174:Sporotrichosis / Q000175:diagnosis / Q000276:immunology* / Q000382:microbiology / Q000662:veterinary*; D015047:Zoonoses / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology
chemical_list: D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D007074:Immunoglobulin G