Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens

Author(s)

Rodrigues, Anderson Messias ^[1] ; Fernandes, Geisa Ferreira ^[1] ; Araujo, Leticia Mendes ^[1] ; Della Terra, Paula Portella ^[1] ; dos Santos, Priscila Oliveira ^[1] ; Pereira, Sandro Antonio ^[2] ; Pacheco Schubach, Tania Maria ^[2] ; Burger, Eva ^[3] ; Lopes-Bezerra, Leila Maria ^[4] ; de Camargo, Zoilo Pires ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Discipline Cellular Biol, Sao Carlos, SP - Brazil

^[2] Fundacao Oswaldo Cruz INI Fiocruz, Inst Nacl Infectol Evandro Chagas, Rio De Janeiro - Brazil

^[3] Univ Fed Alfenas, Dept Microbiol & Immunol, Inst Biomed Sci, Alfenas - Brazil

^[4] Univ Estado Rio de Janeiro, Inst Biol IBRAG, BR-20550011 Rio De Janeiro - Brazil

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 9, n. 8 AUG 2015.
• Web of Science Citations: 15

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. Methodology 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). Principal Findings 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. (AU)

• FAPESP's process: 11/07350-1 - Biology of Sporothrix schenckii complex: Analysis of molecular and proteomics markers, and the role of antigenic and antifungal molecules in sporotrichosis
• Grantee: Anderson Messias Rodrigues
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 09/54024-2 - Molecular biology and proteomics of medically interesting fungi: Paracoccidioides brasiliensis and Sporothrix schenckii
• Grantee: Zoilo Pires de Camargo
• Support Opportunities: Research Projects - Thematic Grants