Evaluation of meningococcal disease isolates for phase variation in pilin adhesion determinants (360G-Wellcome-207223_Z_17_Z)

Neisseria meningitidis is the leading cause of bacterial meningitis. Carriage rates range from 10% for healthy populations to > 30% in at risk populations. Invasive serogroup W (MenW) disease is increasing and has led to inclusion of MenACWY vaccine in the national immunisation schedule. Phase variation allows for alterations in outer membrane protein surface expression through slippage across simple sequence repeats (SSRs), altering the coding frame and truncating the protein or reducing promoter activity. Phase variation within pilC genes affects adhesion and virulence. Preliminary data demonstrates that phase variation is responsible for switching between pilC1 and pilC2 expression during carriage raising the potential for an impact on carriage to disease transitions. Key goals of this project are to analyse and compare phase variation in carriage and invasive MenW isolates. Objective 1: reconstruction of pilC loci through bioinformatics and PCR. Objective 2: analysis of variability in SSRs of pilC genes by alignments and GeneScan analysis. Objective 3: expression states of pilC1 and pilC2 will be determined through bioinformatics. Due to highly similar nature of MenW ST-11 genomes, these data will provide an excellent platform to study pilC phase variation within Neisseria and the effect upon bacterial adherence.