Motilidad y virulencia en el patógeno nosocomial Acinetobacter baumannii

Abstract

Acinetobacter baumannii is a microorganism that causes nosocomial infections and, in recent years, it is becoming a serious health problem worldwide. The emergence of strains resistant to practically all the antimicrobial agents frequently used in the clinic environment turns some infections practically untreatable. With its enormous ability to develop resistances, A. baumannii is also characterized by being able to move through surfaces through a particular little known sort of motility exclusive to this genre, which is known as surface-associated motility. The overall objective of this Doctoral Thesis is the identification of genes involved in this kind of motility, and the study of its relationship with the pathogenicity of A. baumannii. In this work, rifampin-resistant spontaneous mutants presenting altered motility patterns have been isolated and their virulence has been studied in the Caenorhabditis elegans model. In addition, through the analysis of the transcriptional profile between these mutants and the wild-type strain, 6 genes were identified, widely distributed among clinical strains, and whose expression was found decreased in the nonmotile mutants. The construction of mutants and the subsequent phenotypic analysis revealed that the inactivation of 4 of these genes, which encode metabolic enzymes and transporters, causes a reduction in motility and virulence in A. baumannii. Among these genes, a new efflux pump has been identified which, after its functional characterization, has been shown to be involved in the resistance to quinolones. In addition, in order to determine if other expulsion pumps belonging to different families of transporters have a relevant role in the motility and virulence of A. baumannii, mutants of 11 genes were carried out, identifying new transporters that also participate in the pathogenesis of A. baumannii. The results obtained in this Doctoral Thesis show that the inactivation of certain metabolic enzymes and efflux pumps causes a reduction in motility and virulence in A. baumannii. In this way, an abolition of surface-associated motility with an attenuation of virulence in this nosocomial pathogen is clearly related for the first time. In addition, the data obtained in this work open new fronts in the study of new mechanisms of resistance in this microorganism.

Date of Award	25 Oct 2018
Original language	Spanish
Supervisor	Jordi Barbe Garcia (Director) & Jesus Aranda Rodriguez (Director)