Redes de señalización implicadas en la regulación del metabolismo de las ectoínas en la bacteria halófila Chromohalobacter salexigens y su potencial terapéutico como agente neuroprotector

Chromohalobacter salexigens is a halophilic bacterium which naturally produces ectoine and hydroxyectoine, two biotechnologically important compatible solutes that are accumulated in response to osmotic and heat stress, respectively. The exploitation of C. salexigens in biotechnology as a producer of ectoines requires an integral understanding of the regulatory pathways controlling ectoines metabolism. The availability of its genomic sequence, physiological, biochemical, genetic, and high performance transcriptomics data, previously obtained from our Research Group, together with regulatory studies (this work), will allow us to obtain a more global knowledge of the metabolism of the ectoines in C. salexigens. The aim of this PhD was two-fold. On the one hand, to gain insight on the regulatory circuits controlling the metabolism of ectoines in C. salexigens. On the other, to progress in the biomedical use of ectoine for the prevention and treatment of neurodegenerative diseases. The findings presented in this work provide clues for a better understanding of the complex regulation of ectoine metabolism and osmoadaptation in this moderately halophilic bacterium, and its contribution to adaptation to extreme environments. Our results will be overlayed on the existing high-quality genome-based metabolic model and global analyzes, in order to facilitate the rational design of new strains for Systems metabolic engineering. Additionally, we have investigated the in vitro and in vivo application of ectoine as neuroprotective- and inflammation-preventive- treatment in an Aβ murine model of Alzheimer's disease. Thus, we have got more insight in its potential applications in biomedicine, especially in neurodegenerative disorders as Alzheimer’s disease (AD). EupR is the first-described response regulator of a two-component system involved in bacterial osmoregulation (Rodríguez-Moya et al., 2010). Through in silico studies, EupK was selected as its putative cognate histidine kina