A new family of secreted toxins in pathogenic Neisseria species.

Anne Jamet,Daniel Euphrasie,Alexia Ducousso,Alain Charbit,Agnès B. Jousset,Xavier Nassif,Alix Boucharlat,Paulette Mukorako,Eric P. Skaar

doi:10.1371/journal.ppat.1004592

Abstract

The genus Neisseria includes both commensal and pathogenic species which are genetically closely related. However, only meningococcus and gonococcus are important human pathogens. Very few toxins are known to be secreted by pathogenic Neisseria species. Recently, toxins secreted via type V secretion system and belonging to the widespread family of contact-dependent inhibition (CDI) toxins have been described in numerous species including meningococcus. In this study, we analyzed loci containing the maf genes in N. meningitidis and N. gonorrhoeae and proposed a novel uniform nomenclature for maf genomic islands (MGIs). We demonstrated that mafB genes encode secreted polymorphic toxins and that genes immediately downstream of mafB encode a specific immunity protein (MafI). We focused on a MafB toxin found in meningococcal strain NEM8013 and characterized its EndoU ribonuclease activity. maf genes represent 2% of the genome of pathogenic Neisseria, and are virtually absent from non-pathogenic species, thus arguing for an important biological role. Indeed, we showed that overexpression of one of the four MafB toxins of strain NEM8013 provides an advantage in competition assays, suggesting a role of maf loci in niche adaptation.

Highlights

The growing number of sequenced bacterial genomes has led to the computer-based prediction of numerous novel bacterial factors possibly involved in virulence
The recently described CDI system is involved in contact-dependent inhibition of growth and confers to its host strain a significant advantage in competitive ecosystems such as the gastro-intestinal tract
We show that a large family of genes called ‘‘maf’’, found in pathogenic Neisseria species, encodes a toxin-immunity system

Summary

Introduction

The growing number of sequenced bacterial genomes has led to the computer-based prediction of numerous novel bacterial factors possibly involved in virulence. Many novel putative bacterial toxins have been identified by sequence-homology criteria. Aravind and colleagues have recently described widespread genes encoding putative secreted multi-domain toxins grouped under the name of bacterial polymorphic toxin systems (or polymorphic toxinimmunity systems) [1,2,3]. In silico analysis identified over 150 distinct toxin domains in these systems including many putative peptidase, nuclease or deaminase domains. The polymorphic toxin systems are typically encoded on hypervariable chromosomal islands with characteristics of horizontal gene transfer [1].

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Conclusion