Papel del lípido A de Klebsiella pneumoniae en el control de la respuesta inmune

Résumé

K. pneumoniae is a Gram negative bacterium which causes urinary tract infections as well as community-acquired and nosocomial pneumonia. Lipopolysaccharide (LPS) is the major component of the outer membrane of Gram negative bacteria. LPS is a negatively charged polysaccharide anchored to a hydrophobic region, the endotoxic lipid A. In bacteria, two component transduction systems detect environmental changes and trigger the expression of genes responsible for lipid A modifications. Lipid A remodelling helps maintaining cellular integrity, confers resistance to many antimicrobial peptides as well as modulates host’s immune response. Previous results from our laboratory showed that Hfq regulates lipid A modifications in Yersinia enterocolitica O8. In this doctoral thesis we demonstrate that Hfq also regulates lipid A modifications in other Enterobacteriaceae such as Salmonella Typhimurium and K. pneumoniae. In a second study, we have characterised for the first time the lipid A structure expressed by K. pneumoniae in vivo during a lung infection without the need of a previous isolation step on traditional culture media. During the course of a lung infection, K. pneumoniae expresses a lipid A characterised by the presence of a 2-hydroxymiristate as a secondary acylation. Our results show that the lipid A expressed by K. pneumoniae in vivo in the lung is less inflammatory than the lipid A expressed when cultured on traditional culture media. Furthermore, this lipid A found in the lung plays a major role conferring resistance to antimicrobial peptides.