Hypoxia effect on genetic regulation and virulence in Acinetobacter baumannii and Pseudomonas aeruginosa, in vitro and in vivo, and on innate immune response in infections caused by both pathogens
- Autores: María Luisa Gil Marqués
- Directores de la Tesis: Jerónimo Pachón Díaz (dir. tes.), María Eugenia Pachón Ibáñez (dir. tes.), Michael V. Mcconnell (dir. tes.)
- Lectura: En la Universidad de Sevilla ( España ) en 2017
- Idioma: español
- Número de páginas: 239
- Tribunal Calificador de la Tesis: Álvaro Pascual (presid.), Jesús Rodríguez-Baño (secret.), Luis Martinez Martinez (voc.), Harald Seifert (voc.), Manuel Antonio Rodríguez Iglesias (voc.)
- Programa de doctorado: Programa de Doctorado en Biología Molecular, Biomedicina e Investigación Clínica por la Universidad de Sevilla
- Materias:
- Enlaces
- Tesis en acceso abierto en: Idus
- Resumen
The emergence of multi-drug resistant Gram-negative bacilli infections is a well-recognized global health challenge in urgent need of effective solutions. These pathogens cause infections that are very difficult to treat due to the high rate of resistance strains to a lot or even all antimicrobials used in the clinical practice. Furthermore, these kinds of infections are associated to important mortality rates. Unfortunately, the increasing problem of multidrug resistance is not followed by the development of novel antimicrobials. For this reason, there is an important need to develop new strategies to combat multi-drug, extensively-drug and pan-drug resistantGram-negative bacilli.
A new alternative to combat this kind of infections might be blocking specific bacterial virulence factors that bacteria need to infect. It is known that bacteria modulate their gene expression in function of the environment. Therefore, expression of virulence factors can change during the course of infection according to every microenvironment in which bacteria are found. Several studies have reported that hypoxia occurs in a wide range of infection, so it would be interesting to determine the gene profile of these multi-drug resistant pathogens in order to find out new virulence factors that we could block. Moreover, it is also important to know how hypoxia affects to this kind of infection to know better what is happening in vitro and in vivo. Because A. baumannii and P. aeruginosa are two of the most common pathogens that cause healthcare-acquired infection, we have chosen them to study their virulence mechanism under hypoxia in more depth. We have selected the strains A. baumannii ATCC 17978 and P. aeruginosa PAO1 because they are well-known sequenced strains which allow us to analyze virulence factors in a better way.
On the other hand, septic shock patients present tissue hypoxia that might influence the disease. Moreover, septic shock is the most severe complication of sepsis and most studies about this syndrome report a high mortality rate. Hence, it would be useful to study the relationship between tissue hypoxia, HIF-1α levels and immune response, and to determine new biomarkers to predict the outcome.
