The majority of genes in the pathogenic Neisseria species are present in non-pathogenic Neisseria lactamica, including those designated as 'virulence genes'

Abstract

Background: Neisseria meningitidis causes the life-threatening diseases meningococcal meningitis and meningococcal septicemia. Neisseria gonorrhoeae is closely related to the meningococcus, but is the cause of the very different infection, gonorrhea. A number of genes have been implicated in the virulence of these related yet distinct pathogens, but the genes that define and differentiate the species and their behaviours have not been established. Further, a related species, Neisseria lactamica is not associated with either type of infection in normally healthy people, and lives as a harmless commensal. We have determined which of the genes so far identified in the genome sequences of the pathogens are also present in this non-pathogenic related species.

Results: Thirteen unrelated strains of N. lactamica were investigated using comparative genome hybridization to the pan-Neisseria microarray-v2, which contains 2845 unique gene probes. The presence of 127 'virulence genes' was specifically addressed; of these 85 are present in N. lactamica. Of the remaining 42 'virulence genes' only 11 are present in all four of the sequenced pathogenic Neisseria.

Conclusion: Assessment of the complete dataset revealed that the vast majority of genes present in the pathogens are also present in N. lactamica. Of the 1,473 probes to genes shared by all four pathogenic genome sequences, 1,373 hybridize to N. lactamica. These shared genes cannot include genes that are necessary and sufficient for the virulence of the pathogens, since N. lactamica does not share this behaviour. This provides an essential context for the interpretation of gene complement studies of the pathogens.

Figure 1

Hybridization to the pan-Neisseria microarray-v2.

Figure 2

The chromosomal locations of the 6 'virulence genes' present in all pathogenic Neisseria spp. genome sequences, but absent from the N. lactamica genome sequence and for which no N. lactamica strains hybridized to the pan-Neisseria microarray-v2. Panel A: the region between murE and murF contains dca in the pathogen genome sequences and a hypothetical gene in the N. lactamica genome sequence. Panel B: the region between NMB1877 and NMB1884 contains the 'virlence genes' NMB1880 (ABC-P, ABC transport periplasmic substrate-binding protein) and NMB1882 (TonB-dependent receptor) as well as a hypothetical gene (NMB1881) and an araC-like regulator in the pathogen genome sequences, which are all absent in this location in the N. lactamica genome sequence. The probe for NMB1878, the araC regulator hybridized to all N. lactamica strains assessed by CGH; this may be due to another araC-like regulator in another location or the presence of this regulator in this location in all the assessed strains. Panel C: the region between smpB and NMB1524 contains virG in the pathogen genome sequences and a hypothetical gene in the N. lactamica genome sequence. Panel D: the region between trpB and comA contains iga, flanked by Correia Repeat Enclosed Elements (CREE) commonly found in the neisserial genomes; iga and the CREEs are absent in the N. lactamica genome sequence. Panel E: the region between NMB1647 and NMB1645 contains a putative hemolysin encoded by NMB1646 in the pathogenic genome sequences, while in the N. lactamica genome sequence this is the location of lacY and lacZ, which confer the characteristic lactose fermentation phenotype of N. lactamica.