The Respiratory Pathogen <named-content content-type="genus-species">Moraxella catarrhalis</named-content> 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...

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Autores principales: Birendra Singh, Maria Alvarado-Kristensson, Martin Johansson, Oskar Hallgren, Gunilla Westergren-Thorsson, Matthias Mörgelin, Kristian Riesbeck
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Publicado: American Society for Microbiology 2016
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spelling oai:doaj.org-article:a7519fb60dc846e3b321f3428f4d10ea2021-11-15T15:41:41ZThe Respiratory Pathogen <named-content content-type="genus-species">Moraxella catarrhalis</named-content> Targets Collagen for Maximal Adherence to Host Tissues10.1128/mBio.00066-162150-7511https://doaj.org/article/a7519fb60dc846e3b321f3428f4d10ea2016-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00066-16https://doaj.org/toc/2150-7511ABSTRACT 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 the M. catarrhalis UspA2 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. IMPORTANCE 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 of M. catarrhalis is indispensable for bacterial survival in the host, as exemplified by a mouse COPD model.Birendra SinghMaria Alvarado-KristenssonMartin JohanssonOskar HallgrenGunilla Westergren-ThorssonMatthias MörgelinKristian RiesbeckAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 2 (2016)
institution DOAJ
collection DOAJ
language EN
topic Microbiology
QR1-502
spellingShingle Microbiology
QR1-502
Birendra Singh
Maria Alvarado-Kristensson
Martin Johansson
Oskar Hallgren
Gunilla Westergren-Thorsson
Matthias Mörgelin
Kristian Riesbeck
The Respiratory Pathogen <named-content content-type="genus-species">Moraxella catarrhalis</named-content> Targets Collagen for Maximal Adherence to Host Tissues
description 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 the M. catarrhalis UspA2 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. IMPORTANCE 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 of M. catarrhalis is indispensable for bacterial survival in the host, as exemplified by a mouse COPD model.
format article
author Birendra Singh
Maria Alvarado-Kristensson
Martin Johansson
Oskar Hallgren
Gunilla Westergren-Thorsson
Matthias Mörgelin
Kristian Riesbeck
author_facet Birendra Singh
Maria Alvarado-Kristensson
Martin Johansson
Oskar Hallgren
Gunilla Westergren-Thorsson
Matthias Mörgelin
Kristian Riesbeck
author_sort Birendra Singh
title The Respiratory Pathogen <named-content content-type="genus-species">Moraxella catarrhalis</named-content> Targets Collagen for Maximal Adherence to Host Tissues
title_short The Respiratory Pathogen <named-content content-type="genus-species">Moraxella catarrhalis</named-content> Targets Collagen for Maximal Adherence to Host Tissues
title_full The Respiratory Pathogen <named-content content-type="genus-species">Moraxella catarrhalis</named-content> Targets Collagen for Maximal Adherence to Host Tissues
title_fullStr The Respiratory Pathogen <named-content content-type="genus-species">Moraxella catarrhalis</named-content> Targets Collagen for Maximal Adherence to Host Tissues
title_full_unstemmed The Respiratory Pathogen <named-content content-type="genus-species">Moraxella catarrhalis</named-content> Targets Collagen for Maximal Adherence to Host Tissues
title_sort respiratory pathogen <named-content content-type="genus-species">moraxella catarrhalis</named-content> targets collagen for maximal adherence to host tissues
publisher American Society for Microbiology
publishDate 2016
url https://doaj.org/article/a7519fb60dc846e3b321f3428f4d10ea
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