The outer membrane of bacteria contains multiple proteins that are involved with specific interactions with the host’s adhesins. These proteins, including major outer membrane proteins (OMPs), have various roles, including adherence, invasion, and immune evasion. However, despite being broadly characterised as important virulence factors, the precise host ligands that many of these proteins interact with are not known.
This project is exploring the role of multiple cell surface proteins from a variety of bacterial pathogens, including the major nosocomial and drug-resistant pathogen Acinetobacter baumannii, and the human respiratory pathogen nontypeable Haemophilus influenzae (NTHi). Both organisms are World Health Organisation priority pathogens, for which new treatments are urgently required. Selected adhesins from both pathogens have been purified, and the specific host ligands that they bind to investigated using glycan arrays. Following this yes/no binding screen, specific interactions will be characterised and quantified using surface plasmon resonance, SPR. Binding activities will be confirmed using heterologous expression of these adhesins in E. coli, and by the use of specific knock-out mutants of A. baumannii and NTHi.
By this parallel, comprehensive approach to understanding the specific host glycans that the major OMPs from both bacterial pathogens interact with, we will begin to determine if we can use this knowledge to block these interactions. This will be studied using adherence assays and biofilm assays in vitro. Structural analysis and modelling of specific glycan ligands will allow the design and synthesis of glycan mimics to block this interaction, which will be analysed using these adherence and biofilm models.
By understanding the specific glycans that major human pathogens interact with, we will be ideally placed to block this interaction and develop new ways to treat bacterial infections.