Pangenomic analysis reveals metabolic adaptation of Haemophilus parainfluenzae to the urogenital tract

Haemophilus parainfluenzae (Hpar) is a common colonizer found in the upper respiratory tract, although recently urogenital colonization has emerged as a clinical concern. Urogenital Hpar has been associated with increased antibiotic resistance and virulence compared to respiratory Hpar. We analyzed the genome of 270 Hpar isolates, including all sequencing data found in the NCBI sequence read archive database. The pangenome of respiratory and urogenital isolates were compared in order to find potential metabolic or pathogenic adaptations to different host environments. The pangenome-wide association study found significant genomic differences. Specifically, the two-component signal transduction system was significantly enriched in urogenital samples, which could explain the adaptations of Hpar to the unique physico-chemical conditions of the urethra. Additionally, the two-component system could work as a new target for antimicrobials against pathogenic Hpar. The polysaccharide capsule, the main virulence factor in Haemophilus spp. was present in 26/65 of the urogenital samples from our facility, an increase from previous studies. In summary, the data presented suggest that respiratory and urogenital isolates of Hpar belong to different genetic lineages, and therefore it is possible that unprotected oral sex is not the route of transmission of Hpar from the respiratory tract to the urethra. Given the limited amount of available sequences, future studies collecting more isolates from different spatiotemporal locations would shed more light on this issue.