title: Klebsiella pneumoniae outer membrane protein A is required to prevent the activation of airway epithelial cells.
abstract: Outer membrane protein A (OmpA) is a class of proteins highly conserved among the Enterobacteriaceae family and throughout evolution. Klebsiella pneumoniae is a capsulated gram-negative pathogen. It is an important cause of community-acquired and nosocomial pneumonia. Evidence indicates that K. pneumoniae infections are characterized by a lack of an early inflammatory response. Data from our laboratory indicate that K. pneumoniae CPS helps to suppress the host inflammatory response. However, it is unknown whether K. pneumoniae employs additional factors to modulate host inflammatory responses. Here, we report that K. pneumoniae OmpA is important for immune evasion in vitro and in vivo. Infection of A549 and normal human bronchial cells with 52OmpA2, an ompA mutant, increased the levels of IL-8. 52145-Δwca(K2)ompA, which does not express CPS and ompA, induced the highest levels of IL-8. Both mutants could be complemented. In vivo, 52OmpA2 induced higher levels of tnfα, kc, and il6 than the wild type. ompA mutants activated NF-κB, and the phosphorylation of p38, p44/42, and JNK MAPKs and IL-8 induction was via NF-κB-dependent and p38- and p44/42-dependent pathways. 52OmpA2 engaged TLR2 and -4 to activate NF-κB, whereas 52145-Δwca(K2)ompA activated not only TLR2 and TLR4 but also NOD1. Finally, we demonstrate that the ompA mutant is attenuated in the pneumonia mouse model. The results of this study indicate that K. pneumoniae OmpA contributes to attenuate airway cell responses. This may facilitate pathogen survival in the hostile environment of the lung.
authors.affiliation: Laboratory of Microbial Pathogenesis, Fundación Caubet-CIMERA Illes Balears, Recinto Hospital Joan March, Carretera Soller Km 12, 07110 Bunyola, Spain.
authors.forename: Catalina
authors.initials: C
authors.lastname: March
authors.forename: David
authors.initials: D
authors.lastname: Moranta
authors.forename: Verónica
authors.initials: V
authors.lastname: Regueiro
authors.forename: Enrique
authors.initials: E
authors.lastname: Llobet
authors.forename: Anna
authors.initials: A
authors.lastname: Tomás
authors.forename: Junkal
authors.initials: J
authors.lastname: Garmendia
authors.forename: José A
authors.initials: JA
authors.lastname: Bengoechea
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D057131:Immune Evasion / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007710:Klebsiella Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007711:Klebsiella pneumoniae / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D051193:Toll-Like Receptors; C078167:OMPA outer membrane proteins; D020929:Mitogen-Activated Protein Kinase Kinases