Haemophilus influenzae Genome sequencing and assembly

Two cases of severe invasive H. influenzae infection occurred during the same week in the same hospital in San Diego, California – a region where such infections are usually very rare due to vaccine coverage. We thus suspected a local outbreak of an H. influenzae clone not covered by the vaccine. Using whole genome sequencing and phylogenetic analysis of two isolates (H1 and H2, one from each patient), we found that they were distantly related, rapidly ruling out a local outbreak and suggesting independent transmission events. This result highlights the potential for rapid global spread of non-vaccine H. influenzae strains. In this case, both H1 and H2 both encoded a-type capsules, whereas the vaccine targets b-type capsules. We also present comparative genomic evidence that a recent f-type ancestor of H2 acquired an a-type capsule locus from a recent ancestor of H1, and that this horizontal gene transfer (HGT) event likely happened in the past decade in North America, but probably not in the San Diego hospital. These results highlight the potential importance in HGT of the capsule locus in allowing H. influenzae to escape vaccine coverage.