The Respiratory Pathogen Moraxella catarrhalis Targets Collagen for Maximal Adherence to Host Tissues

• Moraxella catarrhalisis 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 inM. catarrhaliscolonization is adherence to the mucosa, epithelial cells, and extracellular matrix (ECM). The objective of this study was to evaluate the role ofM. catarrhalisinteractions 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 ofM. catarrhalisin vivo. We found that allM. catarrhalisclinical isolates tested adhered to fibrillar collagen types I, II, and III and network-forming collagens IV and VI. The trimeric autotransporter adhesinsubiquitoussurfaceproteinA2(UspA2) and UspA2H were identified as major collagen-binding receptors.M. catarrhaliswild 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.IMPORTANCEThe respiratory tract pathogenMoraxella catarrhalisadheres 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 unknownM. catarrhalis-dependent interactions with host collagens and found that the trimeric autotransporter adhesinsubiquitoussurfaceproteinA2(UspA2) and UspA2H are highly important. Our observations also suggested that collagen-mediated adherence ofM. catarrhalisis indispensable for bacterial survival in the host, as exemplified by a mouse COPD model.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

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