Persistence of Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease and Regulation of the Hag/MID Adhesin

Abstract Background Persistence of bacterial pathogens in the airways has profound consequences on the course and pathogenesis of chronic obstructive pulmonary disease (COPD). Patients with COPD continuously acquire and clear strains of Moraxella catarrhalis, a major pathogen in COPD. Some strains a...

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Bibliographic Details
Published in:The Journal of infectious diseases 2019-04, Vol.219 (9), p.1448-1455
Main Authors: Murphy, Timothy F, Brauer, Aimee L, Pettigrew, Melinda M, LaFontaine, Eric R, Tettelin, Hervé
Format: Article
Language:English
Subjects:
Adhesins, Bacterial - genetics
Adult
Bacterial Adhesion
Chronic obstructive pulmonary disease
Colonization
Epithelial cells
Gene Expression
Genomes
Humans
Lung diseases
Major and Brief Reports
Moraxella catarrhalis
Moraxella catarrhalis - genetics
Moraxella catarrhalis - pathogenicity
Moraxella catarrhalis - physiology
Moraxellaceae Infections - microbiology
Obstructive lung disease
Pathogens
Phenotype
Phenotypes
Pulmonary Disease, Chronic Obstructive - microbiology
Respiratory System - microbiology
Strains (organisms)
Virulence
Virulence Factors - genetics
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Summary:Abstract Background Persistence of bacterial pathogens in the airways has profound consequences on the course and pathogenesis of chronic obstructive pulmonary disease (COPD). Patients with COPD continuously acquire and clear strains of Moraxella catarrhalis, a major pathogen in COPD. Some strains are cleared quickly and some persist for months to years. The mechanism of the variability in duration of persistence is unknown. Methods Guided by genome sequences of selected strains, we studied the expression of Hag/MID, hag/mid gene sequences, adherence to human cells, and autoaggregation in longitudinally collected strains of M. catarrhalis from adults with COPD. Results Twenty-eight of 30 cleared strains of M. catarrhalis expressed Hag/MID whereas 17 of 30 persistent strains expressed Hag/MID upon acquisition by patients. All persistent strains ceased expression of Hag/MID during persistence. Expression of Hag/MID in human airways was regulated by slipped-strand mispairing. Virulence-associated phenotypes (adherence to human respiratory epithelial cells and autoaggregation) paralleled Hag/MID expression in airway isolates. Conclusions Most strains of M. catarrhalis express Hag/MID upon acquisition by adults with COPD and all persistent strains shut off expression during persistence. These observations suggest that Hag/MID is important for initial colonization by M. catarrhalis and that cessation of expression facilitates persistence in COPD airways. Moraxella catarrhalis persists in COPD with profound clinical and pathogenetic consequences. Most strains express the major surface antigen Hag/MID on acquisition and then shut off expression, suggesting that Hag/MID is critical for initial colonization and cessation of expression facilitates persistence.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiy680