Nontypeable Haemophilus influenzae (NTHi) is an exclusively human pathobiont that plays a critical role in the course and pathogenesis of
chronic obstructive pulmonary disease (
COPD). NTHi causes acute exacerbations of
COPD and also causes
persistent infection of the lower airways. NTHi expresses four
IgA protease variants (A1, A2, B1, and B2) that play different roles in virulence. Expression of
IgA proteases varies among NTHi strains, but little is known about the frequency and mechanisms by which NTHi modulates
IgA protease expression during
infection in
COPD. To assess expression of
IgA protease during natural
infection in
COPD, we studied
IgA protease expression by 101 persistent strains (median duration of persistence, 161 days; range, 2 to 1,422 days) collected longitudinally from patients enrolled in a 20-year study of
COPD upon initial acquisition and immediately before clearance from the host. Upon acquisition, 89 (88%) expressed
IgA protease. A total of 16 of 101 (16%) strains of NTHi altered expression of
IgA protease during persistence. Indels and slipped-strand mispairing of mononucleotide repeats conferred changes in expression of igaA1, igaA2, and igaB1 Strains with igaB2 underwent frequent changes in expression of
IgA protease B2 during persistence, mediated by slipped-strand mispairing of a 7-nucleotide repeat, TCAAAAT, within the open reading frame of igaB2 We conclude that changes in
iga gene sequences result in changes in expression of
IgA proteases by NTHi during
persistent infection in the respiratory tract of patients with
COPD.