Evidence for capsule switching between carried and disease-causing Neisseria meningitidis strains

Abstract

Changing antigenic structure such as with capsule polysaccharide is a common strategy for bacterial pathogens to evade a host immune system. The recent emergence of an invasive W:2a:P1.7-2,4 sequence type 11 (ST-11) strain of Neisseria meningitidis in New Zealand, an uncommon serogroup/serotype in New Zealand disease cases, was investigated for its genetic origins. Molecular typing of 107 meningococcal isolates with similar serotyping characteristics was undertaken to determine genetic relationships. Results indicated that the W:2a:P1.7-2,4 strain had emerged via capsule switching from a group C strain (C:2a:P1.7-2,4). Neither the upstream nor downstream sites of recombination could be elucidated, but sequence analysis demonstrated that at least 45 kb of DNA was involved in the recombination, including the entire capsule gene cluster. The oatWY gene carried by the W:2a:P1.7-2,4 strain contained the insertion sequence element IS1301, one of five variants of oatWY found in group W135 strains belonging to the carriage-associated ST-22 clonal complex. This suggested that the origin of the capsule genes carried by the invasive W:2a:P1.7-2,4 strain is carriage associated. These results provide novel evidence for the long-standing dogma that disease-associated strains acquire antigenic structure from carriage-associated strains. Moreover, the capsule switch described here has arisen from the exchange of the entire capsule locus.

FIG. 1.

RFLP banding patterns of the W:2a:P1.7-2,4 isolates. The 15 isolates produced multiple banding patterns, with only two groups of identical patterns. Isolate MDU PHL 1 (★) was isolated in Australia in 2003 before the first isolation of the strain in New Zealand.

FIG. 2.

Gene arrangement of the group W135 cps cluster. Regions show the various functional groups within the cluster, as follows: region B (lipid modification genes), region D′ (duplicate LOS biosynthesis operon), region E (putative regulator), region C (capsule transport genes), region A (capsule biosynthesis operon), and region D (LOS biosynthesis operon). Underlined sections represent sequence data collected during the course of this study. Localization of the genes identified with comparative genome hybridizations between the group W135 and group C variants are also identified. NMC0051 and NMC0050 are involved with biosynthesis and O acetylation of the capsule, respectively, and were expected to differ. NMC0038 (NMB0054) and NMC0073 (NMB0088) are located outside the region sequenced (underlined), and further analysis found there to be significant sequence differences in the genes of the two variant strains. The locations marked with a filled star signify the SOR found in a previous study (21).

FIG. 3.

Variants of oatWY found in groups W135 and Y (7).