Genetic Isolation of Meningococci of the Electrophoretic Type 37 Complex

Abstract

Neisseria meningitidis (the meningococcus) is a naturally competent bacterial species in which intra-and interspecific horizontal gene transfer is a major source of genetic diversity. In strains of the electrophoretic type 37 (ET-37) complex and of the A4 cluster, we identified genomic DNA coding for a novel restrictionmodification system and for the tail of a previously unidentified prophage. Furthermore, a novel 7.2-kb DNA segment restricted to clones of the ET-37 complex and the A4 cluster was isolated and shown to occur both as a plasmid (pJS-B) and as a chromosomal integration. Neither the genomic loci nor pJS-B was present in ET-5 complex, lineage 3, or serogroup A meningococci. The differential distribution of the DNA segments described herein, as well as of opcA, porB, nmeAI, nmeBI, and nmeDI described previously, supports the concept of genetic isolation of hypervirulent lineages responsible for most cases of serogroup C disease worldwide.The species Neisseria meningitidis is composed of a large variety of clones and clonal groupings (reviewed in reference 1). The majority of clones colonizing the nasopharynx of humans should be regarded as avirulent (7), and only a few hypervirulent clonal groupings are responsible for the majority of disease in humans. In Europe, serogroup B disease is caused mainly by the electrophoretic type 5 (ET-5) complex and lineage 3 whereas serogroup C disease is caused by the ET-37 complex and the A4 cluster (reviewed in reference 1). Horizontal gene transfer within the naturally competent species and with commensal neisseriae has resulted in genetic variability (2,(11)(12)(13)27), but it has been demonstrated that hypervirulent lineages of both serogroups B and C can be readily distinguished by the presence or absence of several genomic loci; e.g., the ET-5 complex and lineage 3 are characterized by a class 3 porB gene, whereas a class 2 gene is found in the ET-37 complex and the A4 cluster (9, 43). Isotype I of the tbpB gene is restricted to meningococci of the ET-37 complex, while other hypervirulent lineages harbour isotype II (31). Furthermore, the latter lack the gene encoding the adhesin OpcA (32,44).We recently demonstrated a differential distribution of three novel restriction-modification (R-M) systems, nmeAI, nmeBI, and nmeDI (10), while a lineage 3-specific R-M system was described by Bart et al. (3). The differential distribution of meningococcal genes can be caused by rapid expansion of lineages with increased fitness, bottlenecking, periodic selection, and immune selection, which are mechanisms antagonizing the effects of recombination (2,15,16,26,33). In addition, we recently provided evidence that sexual isolation of clonal groupings is caused by differentially distributed R-M systems which partially disrupt genetic transformation (10). In the present study we have extended the list of currently known differentially distributed genes. We compared the ET-37 complex with the ET-5 complex by plasmid profiling and representational difference analysis (RDA). We id...

Phenotypes of a Naturally Defective recB Allele in Neisseria meningitidis Clinical Isolates

“…The recB ET-37 allele-associated transformation defect, although moderate, may contribute to the genetic isolation of meningococci of the ET-37 complex, which has been attributed to specific restriction modification systems (6). Our finding supports the view that this group of bacteria, although easily transformable in the laboratory, incorporates foreign DNA less frequently in nature than serogroup A meningococci do (6,15).…”

Molecular Epidemiological Analysis of the Changing Nature of a Meningococcal Outbreak following a Vaccination Campaign

“…All five serogroup C isolates from the prevaccination period were shown by MLST analysis to be indistinguishable and to belong to the ET-37 complex. All isolates were ST-11, which is characteristic of ET-37 complex isolates (5). Three of the four serogroup B isolates from the postvaccination period were also indistinguishable by MLST analysis and belonged to the ET-5 complex; they were ST-32, a prototype isolate of the ET-5 complex (2).…”

Plasmid Diversity in Neisseriae

“…Limited establishment might result if plasmids more readily integrate into the chromosome in N. meningitidis. Integration of pJS-B into the meningococcal chromosome was shown by Claus and colleagues (5). Differences in the ability to take up extracellular DNA could explain differences in plasmid acquisition.…”

“…Group III consists of three different plasmids, of which two have been isolated from N. lactamica isolates (pNL3.2 and pNL9 [this study]) and one from N. meningitidis (pJS-B [5]). The remaining plasmid was previously identified among isolates from a cluster of hypervirulent N. meningitidis ET-37 (plasmid pJS-B, which can also occur as a chromosomal integration [5]). These plasmids vary considerably in size (ranging from 4 kbp [pNL3.2] to 8.3 kbp [pNL9]), and the genetic organization of the plasmids resembles that of the recently described meningococcal disease-associated (MDA) phage (4) (Fig.…”