Non-typeable Haemophilus influenzea (NTHi) is a human adapted pathogen that is a major source of morbidity and mortality worldwide, with neonatal infants, children and the elderly most at risk. NTHi is a leading bacterial cause of global respiratory infections, and consequently has a major impact on global health care systems. In addition, NTHi infections are a major driver of antibiotic use around the world and increasing antimicrobial resistance is an emerging problem. In order to develop vaccines and therapeutics against NTHi a thorough understanding of NTHi pathogenesis is required. However, due to the incredible diversity exhibited both genotypically and phenotypically by NTHi, there is a significant gap in our understanding of the key proteins NTHi uses to colonise the host and cause disease. The NTHi pangenome encodes a wide variety of proteins involved in multiple stages of colonisation and disease, however the major challenge is identifying proteins that are present in all strains.
This project will characterise a number of NTHi surface proteins: the unstudied protein NTHI1101, the autotransporter Hia and the HMW1/2 adhesins. These proteins have been selected for investigation due to their location on the bacterial cell surface, and high conservation between strains where they are encoded.
Our characterisation of NTHI1101 shows that this protein is required for host cell invasion, but not adherence. Our analysis of Hia and HMW shows that these proteins bind host glycan structures located in the human airway. This work has determined that these major NTHi surface proteins are required for key stages of pathogenesis. Future work will continue our detailed study of these adhesins in order to further understand their precise role in NTHi colonisation and disease.