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

Rajendra Kc,Sanjay S Gautam,Ronan F O'Toole,Nicholas M Harkness,Julia Lachowicz,Gunasegaran Karupiah,Steve Petrovski,Belinda Mcewan,Kelvin W.C Leong,Louise A Cooley

doi:10.1099/mgen.0.000405

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.

Highlights

While nontypeable Haemophilus influenzae (NTHi) is a common commensal of the human nasopharynx, this bacterium is associated with a spectrum of diseases including otitis media and sinusitis, as well as hospital- and community-acquired pneumonia [1]
Sixty-one sequence type (ST) contained more than two Nontypeable Haemophilus influenzae (NTHi) isolates, of which twenty-seven STs were found to be associated with chronic obstructive pulmonary disease (COPD) (Fig. 1b)
A minimum spanning tree (MST) overview of all the isolates was generated by Phyloviz [40] (Fig. 1) using the goeBurst full MST algorithm based on multilocus sequence typing (MLST) profile [39]

Summary

Introduction

While nontypeable Haemophilus influenzae (NTHi) is a common commensal of the human nasopharynx, this bacterium is associated with a spectrum of diseases including otitis media and sinusitis, as well as hospital- and community-acquired pneumonia [1]. Evolutionary and ecological forces drive bacteria to adapt and grow in different niches [6,7,8,9] by utilizing the basic nutrients available and resisting toxic products present in its environment [10]. This evolutionary adaptation typically involves two fundamental processes. A related mechanism is phase variation in which loci susceptible to hypermutation can undergo slipped-s trand mispairing, due to changes in simple sequence repeats, which can rapidly modulate the expression level of genes [7, 12]. The second process is the acquisition of entirely new genetic sequences via horizontal gene transfer, which can undergo homologous

Methods

Results

Conclusion