Characterization of the Maf family of polymorphic toxins in pathogenic Neisseria species

Abstract

In addition to harmless commensal species, Neisseria genus encompasses two pathogenic species, N. meningitidis (the meningococcus) and N. gonorrhoeae (the gonococcus), which are responsible for meningitis and genital tract infections, respectively. Since the publication of the first Neisseria genome in 2000, the presence of several genomic islands (GI) comprising maf genes has been intriguing. These GIs account for approximately 2% of the genome of the pathogenic Neisseria species and the function of the proteins encoded by maf genes remained unknown. We showed that maf genes encode a functional toxin-immunity system where MafB is a toxin neutralized by an immunity protein named MafI. A strain can harbor several MafB/MafI modules with distinct toxic activities. MafB toxins are polymorphic toxins with a conserved N-terminal region and a variable C-terminal region. MafB N-terminal regions consist of a signal peptide and a domain named DUF1020 that is only found in the genus Neisseria. MafB C-terminal regions are highly polymorphic and encode toxic activities. We evidenced the presence of MafB in the culture supernatant of meningococcal cells and we observed a competitive advantage for a strain overexpressing a MafB toxin. Therefore, we characterized a highly variable family of toxin-immunity modules found in multiple loci in pathogenic Neisseria species.

Keywords: MafB; Neisseria; immunity gene; toxin.

Figure 1. FIGURE 1: MafB toxins are involved in growth inhibition of competitor cells.

(A) Genomic organization of mafB and mafI genes. A maf locus contains at least one mafB gene encoding a toxin and one mafI gene encoding the cognate immunity. (B) Competition between an inhibitor cell expressing a MafB toxin and a target cell that either lacks or expresses the cognate immunity protein. MafI immunity proteins (blue squares) encoded by mafI gene found immediately downstream of mafB gene neutralize cognate toxins (red three-quarter circles) whereas other MafI immunity proteins (green oval) do not confer protection.