title: Phase variation of Opa proteins of Neisseria meningitidis and the effects of bacterial transformation.
abstract: Opa proteins are major proteins involved in meningococcal colonization of the nasopharynx and immune interactions. Opa proteins undergo phase variation (PV) due to the presence of the 5'-CTCTT-3' coding repeat (CR) sequence. The dynamics of PV of meningococcal Opa proteins is unknown. Opa PV, including the effect of transformation on PV, was assessed using a panel of Opa-deficient strains of Neisseria meningitidis. Analysis of Opa expression from UK disease-causing isolates was undertaken. Different opa genes demonstrated variable rates of PV, between 6.4 × 10(-4) and 6.9 × 10(-3) per cell per generation. opa genes with a longer CR tract had a higher rate of PV (r(2) = 0.77, p = 0.1212). Bacterial transformation resulted in a 180-fold increase in PV rate. The majority of opa genes in UK disease isolates (315/463, 68.0%) were in the 'on' phase, suggesting the importance of Opa proteins during invasive disease. These data provide valuable information for the first time regarding meningococcal Opa PV. The presence of Opa PV in meningococcal populations and high expression of Opa among invasive strains likely indicates the importance of this protein in bacterial colonization in the human nasopharynx. These findings have potential implications for development of vaccines derived from meningococcal outer membranes.
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford OX3 7LE, UK, manish.sadarangani@paediatrics.ox.ac.uk.
authors.forename: Manish
authors.initials: M
authors.lastname: Sadarangani
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Hoe
authors.forename: Katherine
authors.initials: K
authors.lastname: Makepeace
authors.forename: Peter
authors.initials: P
authors.lastname: van der Ley
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008589:Meningococcal Infections / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D009305:Nasopharynx / Q000382:microbiology / Q000473:pathology; D009345:Neisseria meningitidis / Q000235:genetics* / Q000472:pathogenicity; D014169:Transformation, Bacterial / Q000235:genetics*
chemical_list: D001425:Bacterial Outer Membrane Proteins; C090348:Opa protein, Neisseria