Evolutionary diversification of defensins and cathelicidins in birds and primates

Divergent evolution for more than 310 million years has resulted in an avian immune system that is complex and more compact than that of primates, sharing much of its structure and functions. Not surprisingly, well conserved ancient host defense molecules, such as defensins and cathelicidins, have diversified over time. In this review, we describe how evolution influenced the host defense peptides repertoire, its distribution, and the relationship between structure and biological functions. Marked features of primate and avian HDPs are linked to species-specific characteristics, biological requirements, and environmental challenge

Systemic Administration of Avian Defensin 7: Distribution, Cellular Target, and Antibacterial Potential in Mice

Defensins are natural antimicrobial peptides. The avian beta-defensin AvBD7 isolated from the chicken bone marrow possess broad antibacterial spectrum and strong resistance to proteolysis. However, its ability to fight systemic infections of major concern for public health, such as salmonellosis, is unknown. As a first approach, fluorescence labeling of AvBD7 allowed to track its systemic distribution after intraperitoneal injection in mice using whole body live imaging. It was associated to peritoneal cells and to deeper organs such as the liver. In the next step, the use of labeled AvBD7 allowed to observe its interaction with murine macrophages in culture. After incubation, it was able to penetrate inside the cells through an endocytosis-like mechanism. Furthermore, natural AvBD7 contributed to the control of intracellular multiplication of a multidrug resistant Salmonella strain, after incubation with infected macrophages. Finally, administration in a model of systemic lethal Salmonella infection in mice led to significant improvement of mouse survival, consistently with significant reduction of the liver bacterial load. In conclusion, the results reveal a hitherto unknown intracellular antibacterial effect of AvBD7 in Salmonella target cells and support AvBD7 as a candidate of interest for the treatment of infectious diseases caused by multidrug-resistant pathogenic Enterobacteriaceae

Assessment of functional role and of therapeutic application of avian beta-defensins to fight bacterial infection

National audienc

Avian defensins : new way of fighting pathogenic enterobacteriaceae

L’utilisation intensive des antibiotiques a conduit à l’émergence inquiétante de souches bactériennes multi-résistantes, notamment chez les salmonelles et les colibacilles responsables de maladies infectieuses préoccupantes en santé publique et vétérinaire. Les peptides de défense de l’hôte (HDP) constituent les effecteurs antimicrobiens essentiels de l’immunité innée des animaux. La principale famille d’HDPs chez les oiseaux sont les défensines aviaires, dont deux membres (AvBD2 et AvBD7) isolés de la moelle osseuse du poulet présentent un large spectre antibactérien et constituent ainsi des molécules candidates alternatives aux antibiotiques. Pour démontrer l’intérêt thérapeutique de l’AvBD2 et de l’AvBD7, nous avons (1) prouvé leur efficacité antibactérienne in vitro contre des souches cliniques multirésistantes, (2) montré leur stabilité structurale et fonctionnelle face aux protéases digestives majeures, (3) mis en évidence un nouvel effet antimicrobien dans les macrophages infectés, et finalement (4) prouvé le concept thérapeutique en réduisant la mortalité et la charge bactérienne après injection d’AvBD7 dans un modèle de salmonellose systémique létale chez la souris.Large-scale use of antibiotics has leaded to the emergence of multi drug resistant bacterial strains, particularly in the genus Salmonella and Escherichia coli responsible for infectious diseases outbreaks. This constitutes a major veterinary and public health concern. Host defense peptides (HDPs) represent major effector molecules of the animal’s innate immune system. In birds, the main family of HDPs is composed of avian defensins whose two members (AvBD2 and AvBD7) isolated from chicken bone marrow exhibit large spectrum antibacterial activity. Thus, they both constitute potential candidate molecules as alternative to antibiotics. To demonstrate the therapeutic interest of AvBD2 and AvBD7, we have (1) proved their antibacterial efficiency in vitro towards clinical and multi drug resistant bacterial strains, (2) shown their functional and structural stability when facing major digestive proteases, (3) identified a novel antibacterial effect in infected macrophages, and finally (4) proved the therapeutic concept by reducing mortality and bacterial load after AvBD7 injection in a murine model of lethal salmonellosis

Les défensines aviaires : nouveau moyen de lutte contre les entérobactéries pathogènes

L'utilisation intensive des antibiotiques a conduit à l'émergence inquiétante de souches bactériennes multi-résistantes, notamment chez les salmonelles et les colibacilles responsables de maladies infectieuses préoccupantes en santé publique et vétérinaire. Les peptides de défense de l'hôte (HDP) constituent les effecteurs antimicrobiens essentiels de l'immunité innée des animaux. La principale famille d'HDPs chez les oiseaux sont les défensines aviaires, dont deux membres (AvBD2 et AvBD7) isolés de la moelle osseuse du poulet présentent un large spectre antibactérien et constituent ainsi des molécules candidates alternatives aux antibiotiques. Pour démontrer l'intérêt thérapeutique de l'AvBD2 et de AvBD7, nous avons (1) prouvé leur efficacité antibactérienne in vitro contre des souches cliniques multirésistantes, (2) montré leur stabilité structurale et fonctionnelle face aux protéases digestives majeures, (3) mis en évidence un nouvel effet antimicrobien dans les macrophages infectés, et finalement (4) prouvé le concept thérapeutique en réduisant la mortalité et la charge bactérienne après injection d' AvBD7 dans un modèle de salmonellose systémique létale chez la souris

Assessment of avian beta-defensins interaction with immune cells

Assessment of avian beta-defensins interaction with immune cells. IIIème Journées annuelles GDR 3625 MuFoPA

Robustness and efficiency of avian beta defensins as novel antiinfectious agents

National audienc

Assessment of avian beta-defensins interaction with chicken cells

International audienc

Therapeutic potential of avian beta-defensins in experimental murine salmonellosis

National audienc

Therapeutic of avian beta-defensins in experimental murine salmonellosis

National audienc