Assuntos
Medicina de Emergência/organização & administração , Serviço Hospitalar de Emergência/organização & administração , Sistemas Automatizados de Assistência Junto ao Leito/organização & administração , Guias de Prática Clínica como Assunto , Ultrassonografia Doppler/estatística & dados numéricos , Canadá , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Padrões de Prática Médica/normas , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Sociedades Médicas , Ultrassonografia Doppler/métodosRESUMO
Avian pathogenic Escherichia coli (APEC) causes respiratory disease and sepsis in poultry. To persist in its host, E. coli requires essential nutrients including iron. Since iron is limited in extra-intestinal tissues, E. coli produces siderophores, small molecules with high affinity for ferric iron, to sequester this essential nutrient. To counter bacterial siderophore systems, mammalian hosts secrete siderocalin (also called lipocalin 2 or NGAL), which binds ferric-siderophore complexes rendering them unavailable to bacteria. In humans and mice, siderocalin is known to play a role in primary defense against bacterial infections. In poultry, 4 proteins display homology to the human NGAL (CALß, CALγ, Ggal-C8GC and Ex-FABP). The function and expression of the genes coding for these 4 proteins during infection by APEC is still unknown. Expression levels of these genes were determined by quantitative RT-PCR using RNA extracted from lungs, livers and spleens of healthy 3-week-old chickens and chickens infected with APEC. The gene coding for Ex-FABP was overexpressed in all organs tested. It was significantly more overexpressed in the lungs and liver than in the spleen (37.3 and 27.3 times versus 11.5 times, respectively). The genes coding for Calß and Calγ were also found significantly overexpressed in the liver (27 and 8.2 times, respectively). To confirm the function of Ex-FABP as a siderocalin, the gene coding for this protein was cloned in an expression vector and the protein was purified. In vitro growth inhibition of E. coli strains by Ex-FABP was assayed in parallel with growth inhibition caused by human siderocalin. Purified Ex-FABP inhibited growth of E. coli K-12, which only produces the siderophore enterobactin. However, E. coli strains producing pathogen-associated siderophores including salmochelins (glucosylated enterobactin), aerobactin and yersiniabactin grew normally in the presence of Ex-FABP. These results indicate that Ex-FABP is an avian siderocalin with a siderophore-binding activity similar to that of human siderocalin and that pathogen-specific siderophores are required by APEC to overcome this innate defense protein in poultry.
