RESUMEN
Enterotoxigenic Escherichia coli (ETEC) causing post-weaning diarrhea (PWD) in piglets have a detrimental impact on animal health and economy in pig production. ETEC strains can adhere to the host's small intestinal epithelial cells using fimbriae such as F4 and F18. Phage therapy could represent an interesting alternative to antimicrobial resistance against ETEC infections. In this study, four bacteriophages, named vB_EcoS_ULIM2, vB_EcoM_ULIM3, vB_EcoM_ULIM8 and vB_EcoM_ULIM9, were isolated against an O8:F18 E. coli strain (A-I-210) and selected based on their host range. These phages were characterized in vitro, showing a lytic activity over a pH (4-10) and temperature (25-45 °C) range. According to genomic analysis, these bacteriophages belong to the Caudoviricetes class. No gene related to lysogeny was identified. The in vivo Galleria mellonella larvae model suggested the therapeutic potential of one selected phage, vB_EcoS_ULIM2, with a statistically significant increase in survival compared to non-treated larvae. To assess the effect of this phage on the piglet gut microbiota, vB_EcoS_ULIM2 was inoculated in a static model simulating the piglet intestinal microbial ecosystem for 72 h. This study shows that this phage replicates efficiently both in vitro and in vivo in a Galleria mellonella model and reveals the safety of the phage-based treatment on the piglet microbiota.
Asunto(s)
Bacteriófagos , Escherichia coli Enterotoxigénica , Infecciones por Escherichia coli , Microbioma Gastrointestinal , Enfermedades de los Porcinos , Animales , Porcinos , Escherichia coli Enterotoxigénica/genética , Ecosistema , Infecciones por Escherichia coli/terapia , Infecciones por Escherichia coli/veterinariaRESUMEN
Delayed Graft Function (DGF) is defined as the need for dialysis during the first week after transplantation. DGF is frequent and mostly derived from the ischemia/reperfusion cascade to which the graft is subjected throughout the transplantation process. A graft biopsy is recommended after 7 days of DGF to exclude an episode of acute rejection. Note that DGF per se is associated with an increased risk of acute graft rejection, as well as with a shorter long-term graft survival. Several strategies are being studied to mitigate the ischaemic damage, thereby improving graft quality. Among these, cellular therapy using mesenchymal stromal cells (MSC) is promising, in particular via the administration of MSC in the machine perfusion during the preservation of the graft. We will discuss here the different definitions of DGF and the main predictive factors of DGF, as well as the impact on the graft outcomes. The current strategies to prevent DGF will be briefly reviewed.
La reprise retardée de fonction du greffon rénal (DGF en anglais pour Delayed Graft Function), définie notamment par la nécessité de dialyse durant la 1ère semaine après transplantation, reste un événement fréquent. La DGF résulte principalement des phénomènes d'ischémie/reperfusion auxquels le greffon est soumis tout au long du processus de transplantation. Néanmoins, une biopsie du greffon est préconisée après 7 jours de DGF afin d'exclure une cause non ischémique telle qu'un rejet aigu. La DGF est per se associée à un risque accru de rejet du greffon, ainsi qu'à une moins bonne survie du greffon rénal au long cours. Plusieurs stratégies sont étudiées afin d'atténuer les dommages ischémiques et améliorer la qualité du greffon. Parmi celles-ci, la thérapie cellulaire par cellules stromales mésenchymateuses est prometteuse, notamment via l'administration de celles-ci dans la machine de perfusion lors de la préservation du greffon. Nous aborderons les différentes définitions de la DGF ainsi que ses principaux facteurs prédictifs, l'impact sur le devenir du greffon et, brièvement, les stratégies actuelles dans le cadre de la prévention de la DGF.
