Et tu, Neisseria? Conflicts of Interest Between Neisseria Species

Abstract

Neisseria meningitidis and Neisseria gonorrhoeae are two obligate human pathogens that have evolved to be uniquely adapted to their host. The meningococcus is frequently carried asymptomatically in the nasopharynx, while gonococcal infection of the urogenital tract usually elicits a marked local inflammatory response. Other members of the Neisseria genus are abundant in the upper airway where they could engage in co-operative or competitive interactions with both these pathogens. Here, we briefly outline the potential sites of contact between Neisseria spp. in the body, with emphasis on the upper airway, and describe the growing yet circumstantial evidence for antagonism from carriage studies and human volunteer challenge models with Neisseria lactamica. Recent laboratory studies have characterized antagonistic mechanisms that enable competition between Neisseria species. Several of these mechanisms, including Multiple Adhesin family (Mafs), Two Partner Secretion Systems, and Type VI secretion system, involve direct contact between bacteria; the genetic organisation of these systems, and the domain structure of their effector molecules have striking similarities. Additionally, DNA from one species of Neisseria can be toxic to another species, following uptake. More research is needed to define the full repertoire of antagonistic mechanisms in Neisseria spp., their distribution in strains, their range of activity, and contribution to survival in vivo. Understanding the targets of effectors could reveal how antagonistic relationships between close relatives shape subsequent interactions between pathogens and their hosts.

Keywords: Neisseria; antagonism; commensal; growth inhibition; pathogen.

Figure 1

Schematic of genomic organization of polymorphic toxin system loci found in Neisseria species. Examples of a Maf genomic island, a TPS island and T6SS associated effectors are shown. MGI-1 is the consensus organization of this island (Arenas et al., 2015; Jamet et al., 2015), whereas the TPS island and T6SS locus indicated are from N. meningitidis (Nm) FAM18 (Arenas et al., 2013) and N. cinerea CCUG346T (Custodio et al., 2021), respectively. The secretion elements of the Maf and Tps toxins are different between systems but are generally located in the 5’-end of the genomic islands. mafB includes a region encoding a domain of unknown function named DUF1020, tpsA includes a region encoding a filamentous hemagglutinin adhesin (FHA) domain, whereas T6SS effector genes like those described in N. cinerea (Nc) include regions encoding Rearrangement Hot Spot (RHS) domains. The repertoire of toxin genes is diverse, but each is followed by a gene encoding a cognate immunity protein.

Figure 2

Schematic overview of antagonism systems in Neisseria. Experimentally validated growth inhibitory activities of different Neisseria species are shown. Commensal Neisseria species (N. mucosa, N. cinerea and N. elongata) are shown in purple, Neisseria gonorrhoeae (red), and Neisseria meningitidis (blue) in both capsulated (with grey outline) and unencapsulated form (without grey outline) are shown. The various mediators of growth inhibition/killing are indicated, with arrows pointing from the attacker to the prey cell based on current in vitro experimental evidence. Potential bacteriocins are indicated with a question mark.