María del Mar Blanco

Concise synthesis of tetrahydro derivatives of the pyrido[2,3-b]acridine and pyrido[3,2-b]acridine ring systems

Abstract 5,6,7,8-Tetrahydro-1,4-acridinequinones were readily prepared by Friedlander reaction between cyclohexanone and 2-amino-3,6-dimethoxybenzaldehydes or 2-amino-3,6-dimethoxyacetophenones, followed by oxidative demethylation. Their Diels-Alder reactions with 1-dimethylamino-1-azadienes gave pyrido[3,2- b ]acridines in a regioselective fashion. The regiochemistry of the cycloaddition could be inverted through the introduction of a bromine atom at the C-5 position, to give pyrido[2,3- b ]acridines. The latter ring system is a structural fragment common to several polyciclic marine natural products with antitumour properties, including ascididemin, eilatin and biemnadin.

Analysis of the genome content of Lactococcus garvieae by genomic interspecies microarray hybridization.

BackgroundLactococcus garvieae is a bacterial pathogen that affects different animal species in addition to humans. Despite the widespread distribution and emerging clinical significance of L. garvieae in both veterinary and human medicine, there is almost a complete lack of knowledge about the genetic content of this microorganism. In the present study, the genomic content of L. garvieae CECT 4531 was analysed using bioinformatics tools and microarray-based comparative genomic hybridization (CGH) experiments. Lactococcus lactis subsp. lactis IL1403 and Streptococcus pneumoniae TIGR4 were used as reference microorganisms.ResultsThe combination and integration of in silico analyses and in vitro CGH experiments, performed in comparison with the reference microorganisms, allowed establishment of an inter-species hybridization framework with a detection threshold based on a sequence similarity of ≥ 70%. With this threshold value, 267 genes were identified as having an analogue in L. garvieae, most of which (n = 258) have been documented for the first time in this pathogen. Most of the genes are related to ribosomal, sugar metabolism or energy conversion systems. Some of the identified genes, such as als and mycA, could be involved in the pathogenesis of L. garvieae infections.ConclusionsIn this study, we identified 267 genes that were potentially present in L. garvieae CECT 4531. Some of the identified genes could be involved in the pathogenesis of L. garvieae infections. These results provide the first insight into the genome content of L. garvieae.

Experimental Lactococcus garvieae infection in zebrafish and first evidence of its ability to invade non-phagocytic cells.

Zebrafish has been used for studying infections and host-pathogen interactions in different bacterial fish pathogens. In the present study we evaluated the ability of Lactococcus garvieae to infect zebrafish when inoculated intraperitoneally with 2 × 10(7)UFC of this pathogen. L. garvieae can colonize and invade zebrafish at multiple anatomical sites causing a lethal acute septicemic infection with clinical signs and lesions consistent with those observed in lactococcosis outbreaks. Immunohistochemical studies showed the presence of L. garvieae into macrophages as well as into non-phagocytic zebrafish cells of liver (hepatocytes). The internalization capacity showed by L. garvieae in zebrafish cells was confirmed in the rainbow trout cell line RTG-2. Our results provide the first evidence that L. garvieae is able to invade non-phagocytic host cells.