期刊
EMBO MOLECULAR MEDICINE
卷 7, 期 8, 页码 1018-1033出版社
WILEY
DOI: 10.15252/emmm.201505088
关键词
antibiotic resistance; asthma; biofilm; Haemophilus influenzae; steroids
资金
- Wellcome Trust [WT100204AIA]
- European Union's Seventh Framework Programme [603038]
- National Institutes of Health [2 R37 AI83256-06]
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.
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