Haemophilus influenzae responds to glucocorticoids used in asthma therapy by modulation of biofilm formation and antibiotic resistance.
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.
['Earl|Chris S|CS|', 'Keong|Teh Wooi|TW|', 'An|Shi-qi|SQ|', 'Murdoch|Sarah|S|', 'McCarthy|Yvonne|Y|', 'Garmendia|Junkal|J|', 'Ward|Joseph|J|', 'Dow|J Maxwell|JM|', 'Yang|Liang|L|', "O'Toole|George A|GA|", 'Ryan|Robert P|RP|']
D000818:Animals D000900:Anti-Bacterial Agents D001249:Asthma D017963:Azithromycin D018441:Biofilms D004195:Disease Models, Animal D024881:Drug Resistance, Bacterial D020869:Gene Expression Profiling D005938:Glucocorticoids D006192:Haemophilus Infections D006193:Haemophilus influenzae D006801:Humans D051379:Mice D013183:Sputum
Haemophilus influenzae asthma biofilm antibiotic resistance steroids