Haemophilus influenzae glucose catabolism leading to production of the immunometabolite acetate has a key contribution to the host airway-pathogen interplay.

Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammatory responses and impaired airway immunity, which provides an opportunistic platform for nontypeable Haemophilus influenzae (NTHi) infection. Clinical evidence supports that the COPD airways present increased concentrations of glucose, which may facilitate proliferation of pathogenic bacteria able to use glucose as a carbon source. NTHi metabolizes glucose through respiration-assisted fermentation, leading to the excretion of acetate, formate and succinate. We hypothesised that such specialized glucose catabolism may be a pathoadaptive trait playing a pivotal role in NTHi airway infection. To find out whether this is true, we engineered and characterized bacterial mutant strains impaired to produce acetate, formate or succinate by inactivating the ackA, pflA and frdA genes, respectively. While inactivation of the pflA and frdA genes only had minimal physiological effects, inactivation of the ackA gene affected acetate produ...