Implicación del sistema SOS y de la proteína RecA en el proceso infectivo de Salmonella enterica sv. Typhimurium

Student thesis: Doctoral thesis


The SOS response is a wide-spread regulatory network in the Bacteria domain. Induction of this response occurs in the presence of DNA lesions and it is targeted to address DNA damage and to allow cell survival. The induction of the SOS response causes an increase in the expression of the genes encoding for the system regulatory proteins, LexA (the transcriptional repressor) and RecA (the activator protein), and an increase in the expression of other genes involved in DNA repair processes, homologous recombination and inhibition of cell division. But the induction of the SOS response is also associated with the expression of toxins, the induction of the lytic cicle of resident prophages, the expression and horizontal dissemination of antibiotic resistances, and the horizontal dissemination of pathogenicity islands and integrating conjugative elements. These data suggest that the SOS system plays a key role during the infection process. Moreover, recA mutants of several pathogenic bacteria are avirulent. This demonstrates that the SOS activator is involved in virulence. However, besides acting as the activator of the SOS system, RecA is primarily responsible for the homologous recombination processes. Due to the dual role of the RecA protein, the decrease in virulence of the recA mutants may be attributed either to the reduction of the recombination frequency, or to the inhibition of the SOS system induction, or to both processes. The aim of this work is to elucidate the role developed by the SOS system and by the RecA protein during the infection process of Salmonella enterica sv. Typhimurium (S. Typhimurium), one of the most important pathogens causing foodborne outbrakes in the world. The results obtained in this work show that the overexpression of the recA gene causes a significant decrease in the fitness of this pathogen. Thus, the expression of this gene must remain at its basal level during the infection process developed by S. Typhimurium. Moreover, the overexpression of the recA gene causes a decrease in the ability of this pathogen to invade epithelial cells and to pass through the intestinal epithelium, two essential processes allowing S. Typhimurium to cause the infection. Furthermore, this work demonstrates that the increase in the intracellular concentration of the RecA protein inhibits swarming motility, a multicellular movement over semisolid surfaces associated with the ability of several pathogens, including S. enterica, to invade epithelial cells. This inhibition is caused by the interaction between the RecA protein and the CheW protein, which is associated to the chemotaxis system. The results exposed in this work increase the number of known cellular processes that are associated to the SOS response, conferring a new role on this system and on the RecA protein as regulators of swarming motility in S. Typhimurium. In this context, the induction of the SOS response in the presence of DNA damaging compounds inhibits this kind of motility, avoiding the exposure of the cells to even higher concentrations of such compounds.
Date of Award29 Jun 2012
Original languageSpanish
SupervisorJordi Barbe Garcia (Director) & Susana Campoy Sanchez (Director)

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