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Whole-genome analyses reveal gene content differences between nontypeable Haemophilus influenzae isolates from chronic obstructive pulmonary disease compared to other clinical phenotypes

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KC, R ORCID: 0000-0002-6403-8919, Leong, KWC, Harkness, NM, Lachowicz, J, Gautam, SJ, Cooley, LA, McEwan, B, Petrovski, S, Karupiah, G ORCID: 0000-0001-6306-4405 and O'Toole, RF 2020 , 'Whole-genome analyses reveal gene content differences between nontypeable Haemophilus influenzae isolates from chronic obstructive pulmonary disease compared to other clinical phenotypes' , Microbial Genomics, vol. 6, no. 8 , pp. 1-12 , doi: 10.1099/mgen.0.000405.

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Abstract

Nontypeable Haemophilus influenzae (NTHi) colonizes human upper respiratory airways and plays a key role in the course and pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (COPD). Currently, it is not possible to distinguish COPD isolates of NTHi from other clinical isolates of NTHi using conventional genotyping methods. Here, we analysed the core and accessory genome of 568 NTHi isolates, including 40 newly sequenced isolates, to look for genetic distinctions between NTHi isolates from COPD with respect to other illnesses, including otitis media, meningitis and pneumonia. Phylogenies based on polymorphic sites in the core-genome did not show discrimination between NTHi strains collected from different clinical phenotypes. However, pan-genome-wide association studies identified 79 unique NTHi accessory genes that were significantly associated with COPD. Furthermore, many of the COPD-related NTHi genes have known or predicted roles in virulence, transmembrane transport of metal ions and nutrients, cellular respiration and maintenance of redox homeostasis. This indicates that specific genes may be required by NTHi for its survival or virulence in the COPD lung. These results advance our understanding of the pathogenesis of NTHi infection in COPD lungs.

Item Type: Article
Authors/Creators:KC, R and Leong, KWC and Harkness, NM and Lachowicz, J and Gautam, SJ and Cooley, LA and McEwan, B and Petrovski, S and Karupiah, G and O'Toole, RF
Keywords: COPD, nontypeable Haemophilus influenzae, pan-genome-wide association studies, whole-genome sequencing
Journal or Publication Title: Microbial Genomics
Publisher: Society for General Microbiology
ISSN: 2057-5858
DOI / ID Number: 10.1099/mgen.0.000405
Copyright Information:

© 2020 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License. (https://creativecommons.org/licenses/by/4.0/deed.ast) This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.

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