Genus-Wide Comparative Genomics Analysis ofNeisseriato Identify New Genes Associated with Pathogenicity and Niche Adaptation ofNeisseriaPathogens

Abstract

N. gonorrhoeae and N. meningitidis, the only two human pathogens of Neisseria, are closely related species. But the niches they survived in and their pathogenic characteristics are distinctly different. However, the genetic basis of these differences has not yet been fully elucidated. In this study, comparative genomics analysis was performed based on 15 N. gonorrhoeae, 75 N. meningitidis, and 7 nonpathogenic Neisseria genomes. Core-pangenome analysis found 1111 conserved gene families among them, and each of these species groups had opening pangenome. We found that 452, 78, and 319 gene families were unique in N. gonorrhoeae, N. meningitidis, and both of them, respectively. Those unique gene families were regarded as candidates that related to their pathogenicity and niche adaptation. The relationships among them have been partly verified by functional annotation analysis. But at least one-third genes for each gene set have not found the certain functional information. Simple sequence repeat (SSR), the basis of gene phase variation, was found abundant in the membrane or related genes of each unique gene set, which may facilitate their adaptation to variable host environments. Protein-protein interaction (PPI) analysis found at least five distinct PPI clusters in N. gonorrhoeae and four in N. meningitides, and 167 and 52 proteins with unknown function were contained within them, respectively.

Atypical, Yet Not Infrequent, Infections with Neisseria Species

“…Comparative genomics of commensal human Neisseria species revealed that these organisms share a large repertoire of virulence-associated alleles with gonococci and meningococci, probably as a consequence of widespread virulence gene exchange amongst them [257,276,277]. A recent genome-wide analysis by Lu et al (2019) [4] compared the genomes of 15 N. gonorrhoeae, 75 N. meningitidis and 7 commensal Neisseria spp. (i.e., three N. lactamica strains and single examples of N. mucosa, N. weaveri, N. zoodegmatis, and N. elongata) to identify genes associated with pathogenicity and niche adaptation.…”

“…Furthermore, abundant Simple Sequence Repeats, the molecular basis for gene phase variation, was found within these gene sets and were therefore regarded as candidates that related to their pathogenicity and ability to adapt to variable host environments [278,279]. Functional annotation analysis partly verified the relationships among them, but no certain functional information was found for at least one-third of the genes for each gene set [4].…”

“…Protein-protein interaction analysis (PPI) of unique gonococcal and meningococcal proteins found at least five and four PPI clusters in N. gonorrhoeae and N. meningitidis, respectively. These were associated mainly with basic substance transport and metabolism, genetic information processing (e.g., replication, transcription and translation), cellular processes (e.g., cell wall/membrane/envelope biogenesis and cell motility), bacteria-environment interactions (e.g., signal transduction, extracellular structures and defense mechanism), nitric oxide metabolic pathways, heme utilization and adhesion systems [4]. These proteins unique to the pathogenic Neisseria spp.…”

“…However, two species have evolved to cause disease in humans and, as such, are the only two human-restricted pathogens of the genus: Neisseria gonorrhoeae and N. meningitidis [3]. These two microorganisms are closely related and yet highly adapted to their respective host niches, causing entirely different clinical pathologies [4].…”

“…It is a reasonable assumption that particular genetic features account for their unique phenotypes, their virulence potential (i.e., the development of accidental versus obligate pathogenicity) and their ability to adapt to their corresponding niche-specific conditions. The molecular bases for these qualities have yet to be wholly elucidated [4,27]. However, isolation of both gonococci and meningococci from sites other than their corresponding natural niches has been reported time and again [28][29][30][31][32].…”