Genetic Study of Capsular Switching between Neisseria meningitidis Sequence Type 7 Serogroup A and C Strains

Abstract

Neisseria meningitidis is a leading cause of septicemia and meningitis worldwide. N. meningitidis capsular polysaccharides have been classified into 13 distinct serogroups which are defined by antibody reactivity and structural analysis, and the capsule plays an important role in virulence. Serogroups A, B, C, W135, and Y have been reported to be clinically important. Several newly identified serogroup C isolates belonging to the unique sequence type 7 (ST-7) were identified in China. Since most ST-7 isolates from China belonged to serogroup A, the newly identified ST-7 serogroup C strains were proposed to have arisen from those belonging to ST-7 serogroup A. In this study, six ST-7 serogroup C and three ST-7 serogroup A isolates were analyzed by pulsed-field gel electrophoresis to confirm their sequence type. In order to clarify the genetic basis of capsular switching between ST-7 serogroup A and C strains, the whole capsular gene clusters and surrounding genes of the two representative ST-7 strains belonging to serogroups A and C, respectively, were sequenced and compared. Potential recombination sites were analyzed using the RDP3 beta software, and recombinationrelated regions in two other ST-7 serogroup A and five ST-7 serogroup C strains were also sequenced and compared to the representative ST-7 serogroup A and C strain sequences.

Genetic Analysis of Neisseria meningitidis Sequence Type 7 Serogroup X Originating from Serogroup A

“…This should have little or no effect on capsular expression, which is in accordance with a previous study (23). Interestingly, there were also insertion sequences (IS1031) within recombination regions in other capsular switching events (8,16). We postulate that the insertion sequences were related to the transfer of the capsule gene locus.…”

“…The capsular switching was caused by recombination of several capsular locus genes. A similar event has been reported between ST-7 serogroups A and C, which involved an even longer capsular locus sequence (16). Both events suggest that N. meningitidis ST-7 serogroup A possesses sufficient ability to transform long DNA sequences.…”

“…Rare capsular switching between serogroup A and other serogroups has been reported, although serogroup A historically has been epidemic for many years (11,12), and the vaccines incorporating its antigens have been used frequently (13)(14)(15). The only study to assess capsular switching from serogroup A to another serogroup (serogroup C) confirmed the probability of capsular switching under natural conditions (16). As expected, capsular switching between serogroups A and C involved a long DNA fragment including multiple capsular genes.…”

“…Both events suggest that N. meningitidis ST-7 serogroup A possesses sufficient ability to transform long DNA sequences. Nevertheless, significantly fewer capsular switching events occurred between serogroup A and other serogroups (16,19) than among other serogroups (5,10,20). The specificity of serogroup A might be explained partially by its genetic structure of the capsular gene locus, which is distinct from those in other serogroups.…”

Genomic Basis of a Polyagglutinating Isolate of Neisseria meningitidis

“…However, the nature of this recombination event was not defined at the genome sequence level. Subsequent studies have also implied probable capsule-switching events based on distinct genetic versus antigenic similarities of different serogroups (4,10,(31)(32)(33).…”