RESUMEN
PURPOSE: Acinetobacter baumannii is an important opportunistic pathogen that causes pneumoniae, urinary tract infections, and/or septicemia in immunocompromised patients. This pathogen is frequently associated with nosocomial outbreaks worldwide and has become particularly problematic because of its prevalence and resistance patterns to several antibiotics. In the present study, we used an immunoproteome-based approach to identify immunogenic proteins located on the surface of A. baumannii for the development of a possible immunotherapy against this devastating bacterial infection. EXPERIMENTAL DESIGN: Sera from patients with A. baumannii infections (n = 50) and from a control group of healthy individuals (n = 3) were analyzed for reactivity against A. baumannii outer membrane proteins (OMPs) using Western blot analysis. To identify potential immunogenic proteins in A. baumannii, OMPs were separated by 2DE, and reactive sera from infected patients were randomly selected and divided into two different pools, each containing 15 sera. Finally, MALDI-TOF/TOF mass spectrometric analysis was employed to identify the corresponding proteins. RESULTS: This analysis identified six immunoreactive proteins: OmpA, Omp34kDa, OprC, OprB-like, OXA-23, and ferric siderophore receptor protein. Notably, these proteins are highly abundant on the bacterial surface and involved in virulence, antibiotic resistance, and growth. CONCLUSIONS AND CLINICAL RELEVANCE: Our results support the notion that the proteins identified in the present immunoproteome study could serve as antigen candidates for the development of vaccines and passive immunotherapies against A. baumannii infections.
Asunto(s)
Infecciones por Acinetobacter/inmunología , Acinetobacter baumannii/inmunología , Proteínas Bacterianas/inmunología , Proteoma/inmunología , Proteómica/métodos , Infecciones por Acinetobacter/sangre , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/fisiología , Proteínas de la Membrana Bacteriana Externa/sangre , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas Bacterianas/sangre , Western Blotting , Electroforesis en Gel Bidimensional , Interacciones Huésped-Patógeno/inmunología , Humanos , Receptores de Superficie Celular/sangre , Receptores de Superficie Celular/inmunología , Reproducibilidad de los Resultados , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
In this first study, a series of mesoionic compounds like 1,3,4-thiadiazolium-2-phenylamine derivatives were synthesized and studied in Leishmania amazonensis. The cytotoxic effects of these compounds on the host cells were investigated and the antileishmanial in vitro activity was compared with other species of Leishmania (Leishmania chagasi and Leishmania braziliensis). The compounds presented lower toxicity in murine macrophages than the reference drug pentamidine. The halogen derivatives 5, 6, 8 and 13 (4-F, 4-Cl, 4-Br and 3-Cl) were the most active compounds among all the species tested.
