title: Role of bacterial surface structures on the interaction of Klebsiella pneumoniae with phagocytes.
abstract: Phagocytosis is a key process of the immune system. The human pathogen Klebsiella pneumoniae is a well known example of a pathogen highly resistant to phagocytosis. A wealth of evidence demonstrates that the capsule polysaccharide (CPS) plays a crucial role in resistance to phagocytosis. The amoeba Dictyostelium discoideum shares with mammalian macrophages the ability to phagocytose and kill bacteria. The fact that K. pneumoniae is ubiquitous in nature and, therefore, should avoid predation by amoebae, poses the question whether K. pneumoniae employs similar means to counteract amoebae and mammalian phagocytes. Here we developed an assay to evaluate K. pneumoniae-D. discoideum interaction. The richness of the growth medium affected the threshold at which the cps mutant was permissive for Dictyostelium and only at lower nutrient concentrations the cps mutant was susceptible to predation by amoebae. Given the critical role of bacterial surface elements on host-pathogen interactions, we explored the possible contribution of the lipopolysaccharide (LPS) and outer membrane proteins (OMPs) to combat phagoyctosis by D. discoideum. We uncover that, in addition to the CPS, the LPS O-polysaccharide and the first core sugar participate in Klebsiella resistance to predation by D. discoideum. K. pneumoniae LPS lipid A decorations are also necessary to avoid predation by amoebae although PagP-dependent palmitoylation plays a more important role than the lipid A modification with aminoarabinose. Mutants lacking OMPs OmpA or OmpK36 were also permissive for D. discoideium growth. Except the LPS O-polysaccharide mutants, all mutants were more susceptible to phagocytosis by mouse alveolar macrophages. Finally, we found a correlation between virulence, using the pneumonia mouse model, and resistance to phagocytosis. Altogether, this work reveals novel K. pneumoniae determinants involved in resistance to phagocytosis and supports the notion that Dictyostelium amoebae might be useful as host model to measure K. pneumoniae virulence and not only phagocytosis.
authors: Laboratory Microbial Pathogenesis, Fundació d'Investigació Sanitària de les Illes Balears (FISIB), Bunyola, Spain.
authors: Catalina
authors: C
authors: March
authors: Victoria
authors: V
authors: Cano
authors: David
authors: D
authors: Moranta
authors: Enrique
authors: E
authors: Llobet
authors: Camino
authors: C
authors: Pérez-Gutiérrez
authors: Juan M
authors: JM
authors: Tomás
authors: Teresa
authors: T
authors: Suárez
authors: Junkal
authors: J
authors: Garmendia
authors: José A
authors: JA
authors: Bengoechea
mesh_terms: D000818:Animals; D001089:Arabinose / Q000031:analogs & derivatives / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D002240:Carbohydrate Sequence; D004023:Dictyostelium / Q000382:microbiology / Q000502:physiology; D005260:Female; D054884:Host-Pathogen Interactions; D007711:Klebsiella pneumoniae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D008050:Lipid A / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000166:cytology / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D019081:O Antigens / Q000737:chemistry / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D010586:Phagocytes / Q000166:cytology / Q000382:microbiology*; D010587:Phagocytosis; D018272:Porins / Q000235:genetics
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D008050:Lipid A; D019081:O Antigens; C092233:OmpK36 protein, Klebsiella pneumoniae; D018272:Porins; C016982:aminoarabinose; C078167:OMPA outer membrane proteins; D019308:Palmitic Acid; D001089:Arabinose