Comparative genomic analysis of the Tribolium immune system

The annotation, and comparison with homologous genes in other species, of immunity-related genes in the Tribolium castaneum genome allowed the identification of around 300 candidate defense proteins, and revealed a framework of information on Tribolium immunity

Crystal Structure of Diedel, a Marker of the Immune Response of Drosophila melanogaster

Background: The Drosophila melanogaster gene CG11501 is up regulated after a septic injury and was proposed to act as a negative regulator of the JAK/STAT signaling pathway. Diedel, the CG11501 gene product, is a small protein of 115 residues with 10 cysteines. Methodology/Principal Findings: We have produced Diedel in Drosophila S2 cells as an extra cellular protein thanks to its own signal peptide and solved its crystal structure at 1.15 A ˚ resolution by SIRAS using an iodo derivative. Diedel is composed of two sub domains SD1 and SD2. SD1 is made of an antiparallel b-sheet covered by an a-helix and displays a ferredoxin-like fold. SD2 reveals a new protein fold made of loops connected by four disulfide bridges. Further structural analysis identified conserved hydrophobic residues on the surface of Diedel that may constitute a potential binding site. The existence of two conformations, cis and trans, for the proline 52 may be of interest as prolyl peptidyl isomerisation has been shown to play a role in several physiological mechanisms. The genome of D. melanogaster contains two other genes coding for proteins homologous to Diedel, namely CG43228 and CG34329. Strikingly, apart from Drosophila and the pea aphid Acyrthosiphon pisum, Diedel-related sequences were exclusively identified in a few insect DNA viruses of the Baculoviridae and Ascoviridae families. Conclusion/Significance: Diedel, a marker of the Drosophila antimicrobial/antiviral response, is a member of a small famil

Pathologies tissu spécifiques induites par deux virus à ARN chez la Drosophile

Les insectes sont exposés dans leur environnement à de nombreux virus, et ces infections peuvent avoir un impact économique ou médical. Peu de choses sont connues sur les mécanismes physiopathologiques impliqués dans la susceptibilité aux infections virales. Nous avons utilisé l'organisme modèle drosophile pour étudier la pathologie induite par deux virus à ARN: le virus C de la drosophile (DCV) et le Flock House virus (FHV). La comparaison du transcriptome de mouches infectées par ces deux virus montre que l infection par le DCV conduit à la forte répression de plusieurs centaines de gènes, principalement exprimés dans l intestin moyen des mouches. Parmi eux, plusieurs sont également réprimés dans des conditions jeûne, ce qui suggère que les mouches infectées cessent de se nourrir. Cependant, les mouches infectées par les DCV continuent à se nourrir et leur poids augmente. Cela est dû à une excrétion diminuée, associée à une obstruction dans l'intestin moyen de la mouche. La pathologie induite par le DCV est due à la présence du virus dans un tissu particulier, plutôt que de l'effet néfaste de la réponse immunitaire de l'hôte. Nous avons identifié le gène dSUR, codant la sous-unité d'un canal potassium ATP dépendant (KATP). dSUR est exprimé dans le cœur des mouches, et les mutants pour ce gène sont plus sensibles à l infection par le FHV et contiennent des charges virales plus élevées que les témoins. Nous avons montré que FHV est cardiotropique et que l'activité des KATP cardiaques est liée au mécanisme antiviral de l'interférence ARN. Nous montrons que DCV et FHV, qui semblent très similaires à première vue, induisent des pathologies très différentes chez la drosophile.Insects are exposed in their environement to many viruses, and these infections can have a significant economic or medical impact. At present, little is known about the pathophysiological mechanisms involved in susceptibility to viral infections. We used the model organism Drosophila melanogaster to study the pathology induced by two RNA viruses: the Drosophila C virus (DCV) and the Flock House Virus (FHV).We compared the transcriptome of DCV and FHV-infected flies by using genome-wide microarrays. DCV infection leads to the strong repression of several hundred of genes, mainly expressed in the midgut of the fly. Many genes repressed by the DCV are also repressed under conditions of starvation, suggesting that infected flies stop feeding. However, DCV-infected flies continue to feed and gain weight until their death. This is due to decreased excretion, associated with an intestinal obstruction in the anterior midgut of the fly that probably occurs at the level of the cardia. The pathology induced by DCV results from the presence of the virus in a particular tissue, rather than from the adverse effect of the host s immune response. On the other hand, we identified the gene dSUR, which encode the subunit of an ATP-dependent potassium channel (KATP). dSUR is expressed in the Drosophila heart and mutants for this gene are more sensitive to FHV and contain higher viral loads than controls. We showed that FHV is cardiotropic virus and that the cardiac KATP activity is related to the major antiviral mechanism RNA interference. Our work shows that DCV and FHV, which appear very similar at first sight, induce very different, organ-specific pathologies in Drosophila.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Isolement de substances antimicrobiennes d'insectes (Synthèse chimique et préparation d'analogues structuraux)

Résumé français : notice = 7Ko MAXIMUM : résumé trop long empêche la validation : longueur = 1700 caractéresRésumé anglais : idemSTRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

NF-κB in the Immune Response of Drosophila

The nuclear factor κB (NF-κB) pathways play a major role in Drosophila host defense. Two recognition and signaling cascades control this immune response. The Toll pathway is activated by Gram-positive bacteria and by fungi, whereas the immune deficiency (Imd) pathway responds to Gram-negative bacterial infection. The basic mechanisms of recognition of these various types of microbial infections by the adult fly are now globally understood. Even though some elements are missing in the intracellular pathways, numerous proteins and interactions have been identified. In this article, we present a general picture of the immune functions of NF-κB in Drosophila with all the partners involved in recognition and in the signaling cascades

Solution structure of drosomycin, the first inducible antifungal protein from insects

International audienceDrosomycin is the first antifungal protein characterized recently among the broad family of inducible peptides and proteins produced by insects to respond to bacterial or septic injuries. It is a small protein of 44 amino acid residues extracted from Drosophila melanogaster that exhibits a potent activity against filamentous fungi. Its three-dimensional structure in aqueous solution was determined using 1H 2D NMR. This structure, involving an alpha-helix and a twisted three-stranded beta-sheet, is stabilized by three disulfide bridges. The corresponding Cysteine Stabilized alpha beta (CS alpha beta) motif, which was found in other defense proteins such as the antibacterial insect defensin A, short- and long-chain scorpion toxins, as well as in plant thionins and potent antifungal plant defensins, appears as remarkably persistent along evolution