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Infect Immun. 2019 Oct 18;87(11). pii: e00462-19. doi: 10.1128/IAI.00462-19. Print 2019 Nov.

Discovery and Contribution of Nontypeable Haemophilus influenzae NTHI1441 to Human Respiratory Epithelial Cell Invasion.

Author information

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

Abstract

Nontypeable Haemophilus influenzae (NTHi) is the primary cause of bacterially induced acute exacerbations of chronic obstructive pulmonary disease (COPD). NTHi adheres to and invades host respiratory epithelial cells as a means to persist in the lower airways of adults with COPD. Therefore, we mined the genomes of NTHi strains isolated from the airways of adults with COPD to identify novel proteins to investigate their role in adherence and invasion of human respiratory epithelial cells. An isogenic knockout mutant of the open reading frame NTHI1441 showed a 76.6% ± 5.5% reduction in invasion of human bronchial and alveolar epithelial cells at 1, 3, and 6 h postinfection. Decreased invasion of the NTHI1441 mutant was independent of either intracellular survival or adherence to cells. NTHI1441 is conserved among NTHi genomes. Results of whole-bacterial-cell enzyme-linked immunosorbent assay (ELISA) and flow cytometry experiments identified that NTHI1441 has epitopes expressed on the bacterial cell surface. Adults with COPD develop increased serum IgG against NTHI1441 after experiencing an exacerbation with NTHi. This study reveals NTHI1441 as a novel NTHi virulence factor expressed during infection of the COPD lower airways that contributes to invasion of host respiratory epithelial cells. The role in host cell invasion, conservation among strains, and expression of surface-exposed epitopes suggest that NTHI1441 is a potential target for preventative and therapeutic interventions for disease caused by NTHi.

KEYWORDS:

COPD; NTHi; cell invasion; host-microbe interaction; invasin; persistence; virulence

PMID:
31427451
PMCID:
PMC6803334
[Available on 2020-04-18]
DOI:
10.1128/IAI.00462-19
[Indexed for MEDLINE]

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