Abstract
Haemophilus influenzae is an opportunistic pathogen adapted to the human respiratory tract. Non-typeable H. influenzae are highly heterogeneous, but few studies have analysed the genomic variability of capsulated strains. This study aims to examine the genetic diversity of 37 serotype f isolates from the Netherlands, Portugal, and Spain, and to compare all capsulated genomes available on public databases. Serotype f isolates belonged to CC124 and shared few single nucleotide polymorphisms (SNPs) (n = 10,999), but a high core genome (> 80%). Three main clades were identified by the presence of 75, 60 and 41 exclusive genes for each clade, respectively. Multi-locus sequence type analysis of all capsulated genomes revealed a reduced number of clonal complexes associated with each serotype. Pangenome analysis showed a large pool of genes (n = 6360), many of which were accessory genome (n = 5323). Phylogenetic analysis revealed that serotypes a, b, and f had greater diversity. The total number of SNPs in serotype f was significantly lower than in serotypes a, b, and e (p < 0.0001), indicating low variability within the serotype f clonal complexes. Capsulated H. influenzae are genetically homogeneous, with few lineages in each serotype. Serotype f has high genetic stability regardless of time and country of isolation.
Highlights
Haemophilus influenzae is an opportunistic pathogen adapted to the human respiratory tract
We examine the genomic diversity of H. influenzae serotype f through whole genome sequencing (WGS), using a multicentre collection of colonising and invasive isolates from the Netherlands, Portugal, and Spain
In the multi-locus sequence type (MLST) profile, all isolates belonged to CC124, with most being ST124 (n = 31) and the rest being single-locus variants of ST124, such as ST1739 (n = 2), ST106, ST2390, ST2366, and ST2391 (n = 1, each) (Supplementary Table S1)
Summary
Haemophilus influenzae is an opportunistic pathogen adapted to the human respiratory tract. Non-typeable H. influenzae are highly heterogeneous, but few studies have analysed the genomic variability of capsulated strains. Multi-locus sequence type analysis of all capsulated genomes revealed a reduced number of clonal complexes associated with each serotype. Strains missing the genes for the capsular operon are known as non-typeable H. influenzae (NTHi)[3]. Population structure analysis has shown that capsulated strains are highly clonal and have a limited number of serotype-associated lineages. NTHi appears to have discrete subpopulation structures, but genetic diversity that is ten times greater. This clonality could be related to the presence of capsules and the fact that capsulated strains are more commonly found in invasive disease[13,14]. Few studies have been performed in large datasets of capsulated genomes
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