Assessing the Contributions of the Phase-Variable Sialic Acid and Phosphorylcholine Epitopes of Non-Typeable Haemophilus influenzae to Immunoevasion d

Non-typeable Haemophilus influenzae (NTHi) significantly contribute to human disease including chronic obstructive pulmonary disorder (COPD). This complex disease involves numerous host immune modulators.

Replication of NTHi bacteria in the diseased lung is associated with chronic disease but it is not clear how these bacteria survive host immune responses.

Multiple NTHi genes undergo rapid ON and OFF switching, called phase variation (PV), due to hypermutable repetitive DNA tracts.

Two phase-variable genes drive addition of negatively (sialic acid) and positively (phosphorylcholine) charged epitopes onto the lipooligosaccharide. These molecules influence bacterial interactions with host immune cells.

This project focuses on investigating how PV affects immune evasion in model systems and clinical samples from chronic disease patients. Led by Prof. Chris Bayliss and Dr. Chris Holmes, molecular approaches will be utilized to monitor whether NTHi PV facilitates immune evasion.

Immunological assays, such as resistance to neutrophils, will be developed during sessions at the University of Nottingham with Prof. Luisa Martinez-Pomares. Analysis of clinical COPD samples will be overseen by Prof. Chris Brightling.

These studies will help explain the extent to which PV of surface molecules underlies elicitation of host immune responses and ability of NTHi to survive and cause inflammation in complex chronic diseases.