scholarly journals Identification of Surface Antigens of Moraxella catarrhalis as Targets of Human Serum Antibody Responses in Chronic Obstructive Pulmonary Disease

2005 ◽  
Vol 73 (6) ◽  
pp. 3471-3478 ◽  
Author(s):  
Timothy F. Murphy ◽  
Aimee L. Brauer ◽  
Christoph Aebi ◽  
Sanjay Sethi
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Respiratory Tract ◽  
Pulmonary Disease ◽  
Moraxella Catarrhalis ◽  
Outer Membrane Proteins ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Tract Infections

ABSTRACT Moraxella catarrhalis is an important respiratory tract pathogen, causing otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Adults with COPD make antibody responses to M. catarrhalis following infection, but little is known about the identity of the antigens to which these antibodies are directed. In this study, 12 serum samples obtained from adults with COPD who had cleared M. catarrhalis from the respiratory tract following infection and who had developed new serum immunoglobulin G (IgG) to their infecting strain were subjected to a series of assays to identify the antigens to which potentially protective antibodies were directed. Sera were adsorbed with intact bacterial cells, and antibodies were eluted from the surfaces of the bacteria. Analysis by flow cytometry established that adsorption and elution effectively detected antibodies specifically directed to surface-exposed epitopes. Immunoblot assays of adsorbed and eluted serum fractions were performed with purified outer membranes and purified lipooligosaccharide of homologous infecting strains and with a series of mutants deficient in expression of individual outer membrane proteins (OMPs). While heterogeneity in antibody responses among individuals was observed, five major OMPs, UspA1, UspA2, Hag, TbpB, and OMP CD, were identified as targets of antibodies to surface epitopes in the majority of adults with COPD who cleared the organism. These results have important implications in understanding human immune responses to M. catarrhalis and in elucidating the elements of a protective immune response.

scholarly journals Identification of Domains of the Hag/MID Surface Protein Recognized by Systemic and Mucosal Antibodies in Adults with Chronic Obstructive Pulmonary Disease following Clearance of Moraxella catarrhalis

2009 ◽  
Vol 16 (5) ◽  
pp. 653-659 ◽  
Author(s):  
Eric R. LaFontaine ◽  
Lauren E. Snipes ◽  
Brian Bullard ◽  
Aimee L. Brauer ◽  
Sanjay Sethi ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Respiratory Tract ◽  
Pulmonary Disease ◽  
Moraxella Catarrhalis ◽  
Surface Protein ◽  
Antibody Responses ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Recombinant Peptide ◽  
Mucosal Antibody

ABSTRACT Moraxella catarrhalis is a common cause of respiratory tract infection in the setting of chronic obstructive pulmonary disease (COPD). Adults with COPD acquire and clear strains of M. catarrhalis from the respiratory tract continuously and develop strain-specific protection following clearance of a strain. In previous work, we identified Hag/MID (Moraxella immunoglobulin D-binding protein), a large multifunctional surface protein that acts as an adhesin and hemagglutinin, as a target of antibody responses in adults with COPD after clearance of M. catarrhalis. The goal of the present study was to characterize the domains of Hag/MID to which humans make antibodies, including both systemic and mucosal antibody responses. Analysis of recombinant peptide constructs, which spanned the M. catarrhalis strain O35E Hag/MID protein, with well-characterized serum and sputum samples revealed that most adults with COPD made antibodies directed toward a region of the molecule bounded by amino acids 706 to 863. Serum immunoglobulin G (IgG) and IgA purified from sputum both recognized the same domain. Some flanking sequence of this fragment was necessary for the epitope(s) in this region to maintain its conformation to bind human antibodies. These results reveal that humans consistently generate both systemic and mucosal antibody responses to an immunodominant region of the Hag/MID molecule, which was previously shown to overlap with several biologically relevant domains, including epithelial cell adherence, IgD binding, collagen binding, and hemagglutination.

scholarly journals Impact of Chronic Obstructive Pulmonary Disease on Incidence, Microbiology and Outcome of Ventilator-Associated Lower Respiratory Tract Infections

2020 ◽  
Vol 8 (2) ◽  
pp. 165 ◽  
Author(s):  
Anahita Rouzé ◽  
Pauline Boddaert ◽  
Ignacio Martin-Loeches ◽  
Pedro Povoa ◽  
Alejandro Rodriguez ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Respiratory Tract ◽  
Pulmonary Disease ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Chronic Obstructive ◽  
Lower Respiratory Tract Infections ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Tract Infections

Objectives: To determine the impact of chronic obstructive pulmonary disease (COPD) on incidence, microbiology, and outcomes of ventilator-associated lower respiratory tract infections (VA-LRTI). Methods: Planned ancillary analysis of TAVeM study, including 2960 consecutive adult patients who received invasive mechanical ventilation (MV) > 48 h. COPD patients (n = 494) were compared to non-COPD patients (n = 2466). The diagnosis of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) was based on clinical, radiological and quantitative microbiological criteria. Results: No significant difference was found in VAP (12% versus 13%, p = 0.931), or VAT incidence (13% versus 10%, p = 0.093) between COPD and non-COPD patients. Among patients with VA-LRTI, Escherichia coli and Stenotrophomonas maltophilia were significantly more frequent in COPD patients as compared with non-COPD patients. However, COPD had no significant impact on multidrug-resistant bacteria incidence. Appropriate antibiotic treatment was not significantly associated with progression from VAT to VAP among COPD patients who developed VAT, unlike non-COPD patients. Among COPD patients, patients who developed VAT or VAP had significantly longer MV duration (17 days (9–30) or 15 (8–27) versus 7 (4–12), p < 0.001) and intensive care unit (ICU) length of stay (24 (17–39) or 21 (14–40) versus 12 (8–19), p < 0.001) than patients without VA-LRTI. ICU mortality was also higher in COPD patients who developed VAP (44%), but not VAT(38%), as compared to no VA-LRTI (26%, p = 0.006). These worse outcomes associated with VA-LRTI were similar among non-COPD patients. Conclusions: COPD had no significant impact on incidence or outcomes of patients who developed VAP or VAT.

scholarly journals The Respiratory PathogenMoraxella catarrhalisTargets Collagen for Maximal Adherence to Host Tissues

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Birendra Singh ◽  
Maria Alvarado-Kristensson ◽  
Martin Johansson ◽  
Oskar Hallgren ◽  
Gunilla Westergren-Thorsson ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Respiratory Tract ◽  
Pulmonary Disease ◽  
Moraxella Catarrhalis ◽  
Clinical Isolates ◽  
Lung Fibroblasts ◽  
Chronic Obstructive ◽  
Wild Type ◽  
Collagen Binding ◽  
Obstructive Pulmonary Disease

ABSTRACTMoraxella 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.

scholarly journals A Cation-Binding Surface Protein as a Vaccine Antigen To Prevent Moraxella catarrhalis Otitis Media and Infections in Chronic Obstructive Pulmonary Disease

2017 ◽  
Vol 24 (9) ◽  
Author(s):  
Timothy F. Murphy ◽  
Aimee L. Brauer ◽  
Antoinette Johnson ◽  
Gregory E. Wilding ◽  
Mary Koszelak-Rosenblum ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Respiratory Tract ◽  
Pulmonary Disease ◽  
Otitis Media ◽  
Moraxella Catarrhalis ◽  
Vaccine Antigen ◽  
Chronic Obstructive ◽  
Human Respiratory Tract ◽  
Obstructive Pulmonary Disease ◽  
Content Type

ABSTRACT Moraxella catarrhalis is an exclusively human respiratory tract pathogen that is a common cause of otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease. A vaccine to prevent these infections would have a major impact on reducing the substantial global morbidity and mortality in these populations. Through a genome mining approach, we identified AfeA, an ∼32-kDa substrate binding protein of an ABC transport system, as an excellent candidate vaccine antigen. Recombinant AfeA was expressed and purified and binds ferric, ferrous, manganese, and zinc ions, as demonstrated by thermal shift assays. It is a highly conserved protein that is present in all strains of M. catarrhalis. Immunization with recombinant purified AfeA induces high-titer antibodies that recognize the native M. catarrhalis protein. AfeA expresses abundant epitopes on the bacterial surface and induces protective responses in the mouse pulmonary clearance model following aerosol challenge with M. catarrhalis. Finally, AfeA is expressed during human respiratory tract infection of adults with chronic obstructive pulmonary disease (COPD). Based on these observations, AfeA is an excellent vaccine antigen to be included in a vaccine to prevent infections caused by M. catarrhalis.

Sign in / Sign up

Export Citation Format

Share Document