title: The Respiratory Pathogen Moraxella catarrhalis Targets Collagen for Maximal Adherence to Host Tissues.
abstract: Moraxella catarrhalis is a human respiratory pathogen that causes acute otitis media in children and is associated with exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD). The first step in M. catarrhalis colonization is adherence to the mucosa, epithelial cells, and extracellular matrix (ECM). The objective of this study was to evaluate the role of M. catarrhalis interactions with collagens from various angles. Clinical isolates (n= 43) were tested for collagen binding, followed by a detailed analysis of protein-protein interactions using recombinantly expressed proteins.M. catarrhalis-dependent interactions with collagen produced by human lung fibroblasts and tracheal tissues were studied by utilizing confocal immunohistochemistry and high-resolution scanning electron microscopy. A mouse smoke-induced chronic obstructive pulmonary disease (COPD) model was used to estimate the adherence of M. catarrhalis in vivo. We found that all M. catarrhalis clinical isolates tested adhered to fibrillar collagen types I, II, and III and network-forming collagens IV and VI. The trimeric autotransporter adhesins ubiquitous surface protein A2(UspA2) and UspA2H were identified as major collagen-binding receptors.M. catarrhalis wild type adhered to human tracheal tissue and collagen-producing lung fibroblasts, whereas UspA2 and UspA2H deletion mutants did not. Moreover, in the COPD mouse model, bacteria devoid of UspA2 and UspA2H had a reduced level of adherence to the respiratory tract compared to the adherence of wild-type bacteria. Our data therefore suggest that theM. catarrhalisUspA2 and UspA2H-dependent interaction with collagens is highly critical for adherence in the host and, furthermore, may play an important role in the establishment of disease.
  
  
  OBJECTIVE
  The respiratory tract pathogen Moraxella catarrhalis adheres to the host by interacting with several components, including the ECM. Collagen accounts for 30% of total body proteins, and therefore, bacterial adherence to abundant host collagens mediates bacterial persistence and colonization. In this study, we characterized previously unknown M. catarrhalis-dependent interactions with host collagens and found that the trimeric autotransporter adhesins ubiquitous surface protein A2(UspA2) and UspA2H are highly important. Our observations also suggested that collagen-mediated adherence ofM. catarrhalis is indispensable for bacterial survival in the host, as exemplified by a mouse COPD model.
authors.affiliation: Clinical Microbiology, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Birendra
authors.initials: B
authors.lastname: Singh
authors.affiliation: Molecular Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Alvarado-Kristensson
authors.affiliation: Molecular Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Johansson
authors.affiliation: Respiratory Medicine and Allergology, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
authors.forename: Oskar
authors.initials: O
authors.lastname: Hallgren
authors.affiliation: Respiratory Medicine and Allergology, Department of Experimental Medical Sciences, Lund University, Lund, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Westergren-Thorsson
authors.affiliation: Section of Infectious Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.affiliation: Clinical Microbiology, Department of Translational Medicine, Lund University, Malmö, Sweden kristian.riesbeck@med.lu.se.
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D000818:Animals; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D001936:Moraxella catarrhalis / Q000502:physiology*; D045828:Moraxellaceae Infections / Q000382:microbiology / Q000473:pathology
chemical_list: D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; C089675:UspA protein, Moraxella catarrhalis; D003094:Collagen