Tesis doctoral de Gerard Alvarez Juste
Salmonella enterica ser. Typhimurium (s. Typhimurium) is an enteropathogen able to infect several mammalian species, generally causing mild diseases, such as gastroenteritis, although it can also become a systemic infection, producing septicaemia and even the death of the infected host. like other enterobacteria, the genome of s. Typhimurium codes for alkylation damage repair proteins. This kind of damage appears when alkylating agents, which are present in the environment or are produced endogenously as byproducts of normal metabolism, introduce alkyl groups in the dna bases. Some of the most important genes coding for these proteins are ada, alka, alkb and aidb, which generate the adaptive response to alkylation damage (known as the ada response); and ogt and tag, which are not included in this response but possess similar functions. Other repair systems with a wider range of activities can also repair alkylation damage, being especially important the genes belonging to the global genome repair (ggr, which is carried out by the uvrabc enzymatic complex) and the transcription-coupled dna repair (tcr, focused on the transcriptionally active genes and directed by the mfd protein, which recruits the uvrabc or the mutsl complexes) pathways of the nucleotide excision repair system (ner). Altogether compound a large variety of repair activities which allow the recognition of a broad diversity of targets generated by alkylating agents. in order to establish the role of each of these genes and the consequences of their lack during the infection process, strains defective in one or several of them were constructed. Afterwards, each strain was treated with alkylating agents to analyze its survival. Although s. Typhimurium possesses so many alkylation damage repair proteins, in most strains the survival decreased due to the absence of just one or some of those proteins. Moreover, competitive assays using balb/c mice were performed to determine the fitness of each strain. The results show that, even in those strains defective in several genes, the in vivo fitness of s. Typhimurium is not affected by the lack of most of the alkylation damage repair proteins studied, since only the strain ua1869 defective in the ada, ogt, tag, uvra, and mfd genes presented a reduction of its virulence when it was orally inoculated. Therefore, the amount of alkylating agents generated in the organism might be lower than that used in the in vitro assays. Thus, the evolutionary conservation of the alkylation damage repair genes in s. Typhimurium may be due to survival outside the host. the fact that the fitness decreased in the ua1869 strain and not in other mutants, some of them defective in a larger number of genes, suggests the existence of certain overlap between different repair systems. Thus, the absence of some repair proteins might be compensated by other belonging to other systems apparently different.
Datos académicos de la tesis doctoral «Impacte dels sistemes de reparació de lesions produÁ¯des per agents alquilants en la viruléncia de salmonella enterica ser. typhimurium«
- Título de la tesis: Impacte dels sistemes de reparació de lesions produÁ¯des per agents alquilants en la viruléncia de salmonella enterica ser. typhimurium
- Autor: Gerard Alvarez Juste
- Universidad: Autónoma de barcelona
- Fecha de lectura de la tesis: 05/03/2010
Dirección y tribunal
- Director de la tesis
- Jordi Barbé García
- Tribunal
- Presidente del tribunal: montserrat Llagostera casas
- anna Bigas terricabras (vocal)
- (vocal)
- (vocal)