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

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.

Genomic Diversity and Antimicrobial Resistance of Haemophilus Colonizing the Airways of Young Children with Cystic Fibrosis

“…S4 and S5 online at doi.org/10.26188/14954931). This finding is consistent with prior studies of NTHi which reported finding no evidence for phylogenetic signals of geographical origin (53,54) or clinical source (54,55). However, whole-genome k-mer DAPC revealed distinct clustering of RCH CF isolates with others that were noninvasive, collected from the respiratory tract, isolated from children, and circulating in Australia (based on the respective individual discriminant functions, see Fig.…”

Epidemiology and population structure of Haemophilus influenzae causing invasive disease

“…Based on their clinical characteristics, it was difficult to differentiate NTHi isolates from among each clade since they were clinically diverse, which is consistent with other studies showing no correlation between the phylogenetic classification and clinical or geographical origins [ 12, 45 ]. However, Kc et al [ 46 ] classified NTHi isolates into eight clades in which, despite having COPD strains distributed among all the clades, they could differentiate between COPD and non-COPD strains according to the composition of the accessory genome. This suggests that further studies are needed to improve the classification of NTHi strains and to find an association between the clades, the composition of the accessory genome, clinical data and pathogenesis.…”

Genomic diversity and antimicrobial resistance ofHaemophiluscolonising the airways of young children with cystic fibrosis

“…The Hia and HMW adhesins, Hif pilus, and IgA-proteases are Hi virulence factors that are also differentially present in strains (56,57) and play a role in colonisation of specific niches like the respiratory tract (58–61). Genome-wide association analysis could potentially identify other contributing factors (62), however this is beyond the scope of the present study.…”