Haemophilus influenzae responds to glucocorticoids used in asthma therapy by modulation of biofilm formation and antibiotic resistance

Chris S. Earl, Teh Wooi Keong, Shi-Qi An, Sarah Murdoch, Yvonne McCarthy, Junkal Garmendia, Joseph Ward, J. Maxwell Dow, Liang Yang, George A. O'Toole, Robert P. Ryan (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    Abstract

    Glucocorticosteroids are used as a main treatment to reduce airway inflammation in people with asthma who suffer from neutrophilic airway inflammation, a condition frequently associated with Haemophilus influenzae colonization. Here we show that glucocorticosteroids have a direct influence on the behavior of H. influenzae that may account for associated difficulties with therapy. Using a mouse model of infection, we show that corticosteroid treatment promotes H. influenzae persistence. Transcriptomic analysis of bacteria either isolated from infected mouse airway or grown in laboratory medium identified a number of genes encoding regulatory factors whose expression responded to the presence of glucocorticosteroids. Importantly, a number of these corticosteroid-responsive genes also showed elevated expression in H. influenzae within sputum from asthma patients undergoing steroid treatment. Addition of corticosteroid to H. influenzae led to alteration in biofilm formation and enhanced resistance to azithromycin, and promoted azithromycin resistance in an animal model of respiratory infection. Taken together, these data strongly suggest that H. influenzae can respond directly to corticosteroid treatment in the airway potentially influencing biofilm formation, persistence and the efficacy of antibiotic treatment.

    Original languageEnglish
    Pages (from-to)1018-1033
    Number of pages16
    JournalEmbo Molecular Medicine
    Volume7
    Issue number8
    Early online date20 May 2015
    DOIs
    Publication statusPublished - 1 Aug 2015

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