Estudio de nuevas dianas terapéuticas frente a "Acinetobacter baumannii" mediante análisis transcriptómico "in vivo" y evaluación de nuevas estrategias antimicrobianas

Abstract

Acinetobacter baumannii is a nosocomial pathogen that presents great genetic plasticity and antimicrobial resistance frequently implied hospital outbreaks difficult to control. The study of the genome of this pathogen allows us to select the most interesting genes as possible therapeutic targets. This Thesis presents a global transcriptomic analysis of bacterial RNA isolated directly from the lungs of mice infected with A. baumannii, in order to identify those genes involved in the development of pneumonia infection. hisF and lpxB genes were found to be overexpressed during infection. HisF is involved in lung persistence due to inhibition of macrophage recruitment and IL-6 production by the host. The translation of LpxB, the essential protein involved in the synthesis of LPS, has been inhibited using antisense technology. Colistin, an antibiotic with a high toxicity, is mainly used in the treatment of multi-resistant strains and is considered the last therapeutic option. MD3 is a SPasas inhibitor that presents synergy with colistin, thus being a promising candidate in the treatment of infections caused by A. baumannii, including colistin-resistant strains. In vivo transcriptomic analysis allowed us to identify several genes as potential therapeutic targets and evaluated new strategies and antimicrobial compounds for the treatment of A. baumannii.