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Infect Immun. 2018 Jul 23;86(8). pii: e00313-18. doi: 10.1128/IAI.00313-18. Print 2018 Aug.

Changes in IgA Protease Expression Are Conferred by Changes in Genomes during Persistent Infection by Nontypeable Haemophilus influenzae in Chronic Obstructive Pulmonary Disease.

Author information

1
Department of Microbiology and Immunology, University at Buffalo, Buffalo, New York, USA.
2
Clinical and Translational Research Center, University at Buffalo, Buffalo, New York, USA.
3
Division of Infectious Diseases, Department of Medicine, University at Buffalo, Buffalo, New York, USA.
4
Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, Connecticut, USA.
5
W. M. Keck Foundation Biotechnology Resource Laboratory, Yale School of Medicine, Yale University, New Haven, Connecticut, USA.
6
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, Connecticut, USA.
7
Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
8
Department of Microbiology and Immunology, University at Buffalo, Buffalo, New York, USA murphyt@buffalo.edu.

Abstract

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.

KEYWORDS:

IgA protease; chronic obstructive pulmonary disease; nontypeable Haemophilus influenzae; respiratory tract infections

PMID:
29760213
PMCID:
PMC6056860
[Available on 2019-01-23]
DOI:
10.1128/IAI.00313-18

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