Genome Characterisation of Invasive Haemophilus influenzae in Pregnancy: The Noticeable Placental Tissue Tropism Is Distributed across the Species Rather Than Linked with Capsulation or Particular Clones

Abstract

Pregnancy is associated with a 5-26 times increased risk of invasive Haemophilus influenzae infection and subsequent adverse pregnancy outcomes. Incidence rate and outcome are published in some regions, but the characterisation of bacterial isolates is limited. We performed comparative genomic analyses of isolates from 12 pregnancy-associated cases, cultured from maternal bacteraemia in pregnancy (nine), postpartum bacteraemia (one), neonatal bacteraemia (one), and placental tissue (one). In two bacteraemia cases, identical isolates were also cultured from cervical swabs. Eight cases occurred early in pregnancy (gestational week 7-26), and seven of them resulted in miscarriage or neonatal death. All bacterial genomes were devoid of capsule loci, and they were evenly distributed in the major phylogenetic group I of the species. The conspicuous tropism of H. influenzae for pregnancy and placental tissue is associated with the species rather than specific clonal subtypes.

Keywords: Haemophilus influenzae; abortion; bacteraemia; infection; neonatal; pregnancy; whole-genome sequencing.

Figure 1

Neighbour-joining dendrogram of 425 Haemophilus core genes depicting the relationship the study strains and the taxonomy of closely related species within the genus. Red circles, 14 invasive H. influenzae strains from 12 pregnancies (B and C designate blood and cervix from the same case); orange circles, type strains of validly published species names; open circles, reference strains of H. influenzae phylogenetic group I (see text for details); light blue circles, fastANI reference sequences from GTDB representing putative novel species; green circle, reference strain of “Haemophilus quentini” (not validly published name). Freeform shapes encircle putative species Haemophilus influenzae E and Haemophilus influenzae F. Alignment is based on 351,171 nt; bar represents 2,000 residue substitutions. The asterisks denote new MLST sequence types described in this study.