Investigation of the Genetic Origins of a Novel Meningococcal Strain Causing Invasive Disease

Abstract

Neisseria meningitidis group W135 is under-represented in meningococcal disease in New Zealand with less than 1% of total cases annually. Since 2003, isolates with the novel strain-type W:2a:P1.7-2,4 have been collected from disease cases in New Zealand, contributing to a significant increase in the number of meningococcal W135 disease cases. Of greater interest is the presence of the PorA subtype P1.7-2,4 which is associated with the current group B epidemic strain, B:4:P1.7-2,4. N. meningitidis has high rates of both DNA mutation and recombination resulting in a genetically highly diverse population. This has major implications for the virulence of the organism as antigenic structures can be "switched" allowing a measure of escape from the immune system. The emergence of the W:2a:P1.7-2,4 strain was thought most likely the result of DNA exchange. The primary aim of this study was to determine what DNA had been exchanged to result in the new strain. The original hypothesis was that the W:2a:P1.7-2,4 strain had arisen through a PorA switch from the New Zealand epidemic strain in a W:2a:P1.5,2 strain. Using serological and molecular typing methods including sequencing analysis, whole genome RFLP, and microarray analysis it was found that the W:2a:P1.7-2,4 strain arose from a capsule switch involving at least 45 kb of DNA in a group C strain. This DNA fragment contained the entire group W135 capsule gene cluster. Furthermore, sequencing of oatWY determined that the origins of the group W135 capsule genes are most likely to be from a carriage-associated strain. While the belief that disease-associated strains can acquire DNA from carriage-associated strains is long standing this is the first time that experimental evidence has been demonstrated.