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

Timothy F. Murphy, Aimee L. Brauer, Melinda M. Pettigrew, Eric R. Lafontaine, Hervé Tettelin

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Article numberjiy680
Pages (from-to)1448-1455
Number of pages8
JournalJournal of Infectious Diseases
Volume219
Issue number9
DOIs
StatePublished - Apr 16 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 The Author(s) 2018.

Keywords

  • bacterial genome
  • bacterial pathogenesis
  • chronic obstructive pulmonary disease
  • Moraxella catarrhalis
  • persistent infection
  • respiratory tract infection
  • slipped-strand mispairing

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