Expression of pathogen-like Opa adhesins in commensal Neisseria: genetic and functional analysis

Abstract

Several species of commensal Neisseriae (Cn) may colonize the human nasopharynx, but little is known about their adhesion mechanisms. We have investigated structural and functional similarities between adhesins of Cn and of Neisseria meningitidis (Nm), also a frequent colonizer of the nasopharynx. In this study, we demonstrate the expression of Opa‐like proteins in nine strains of Cn. Phylogenetic analysis segregated the majority of the Cn Opa in a cluster separated from the pathogenic cluster with a few exceptions. One Opa, which located within the pathogenic cluster, was strikingly similar (74%) to an Opa of a Neisseria gonorrhoeae (Ng) strain and, like Ng, it lacked the extra Y11 or the 136DKF138 triplet insert, which are conserved among many N. meningitidis Opa proteins. Most importantly, the majority of the Cn Opa proteins were able to interact with human CEACAM1 (CD66a) molecules, previously identified as receptors for pathogenic Opa proteins. By the use of CEACAM1 N‐domain mutants, we demonstrate that Cn Opa target the same region of the N‐domain of the receptor as that used by Nm. Furthermore, Cn strains bound to cell‐expressed human CEACAM1. In competition assays, adherent Cn strain C450, exhibiting high affinity for CEACAM1, was not displaced by a Nm isolate and vice versa. But in simultaneous incubation, Nm out‐competed the Cn strain. This is the first study to demonstrate the expression of adhesins in Cn that are structurally and functionally closely related to pathogenic adhesins. The studies imply that some Cn have the potential to occupy and thus compete with the pathogens for receptors on human mucosa, their common and exclusive niche.

Profiling of bacterial adhesin — host receptor recognition by soluble immunoglobulin superfamily domains

“…Phase variation of individual Opa proteins occurs at a frequency of ∼ 10 − 3 and results in a heterogeneous population of bacteria expressing none, one or multiple Opa proteins. Interestingly, recent studies from Toleman et al (2001) demonstrated the expression of Opa-like proteins in diverse commensal strains of Neisseria, including N. lactamica and N. subflava. Besides a few Opa protein variants that recognize cell surface expressed heparansulfate proteoglycans (Opa HSPG ) (Chen et al, 1995;van Putten and Paul, 1995), most Opa proteins of diverse strains of Nme and Ngo recognize one or more members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family (Chen and Gotschlich, 1996;Gray-Owen et al, 1997a;Virji et al, 1996b).…”

Characterization of the Moraxella catarrhalis Opa-Like Protein, OlpA, Reveals a Phylogenetically Conserved Family of Outer Membrane Proteins

“…Human CEACAM1 is also engaged by the adhesins of other bacteria, including the Haemophilus influenzae P5 protein (14) and the Opa proteins of pathogenic and commensal Neisseria spp. (12,29,35). Remarkably, the UspA1, P5, and Opa proteins are not related, indicating a clear example of convergent evolution by these various human-restricted bacteria.…”

Relative Contributions of Recombination and Mutation to the Diversification of the opa Gene Repertoire of Neisseria gonorrhoeae

“…Isolates of Neisseria meningitidis have three or four opa genes (1), while most commensal species have only one gene, with the exception of Neisseria lactamica, which has been reported to have two (34). In N. gonorrhoeae, which is believed to have arisen relatively recently as a lineage of one of the above nasopharyngeal neisseriae that can colonize and be transmitted from the genital tract, there appears to have been an expansion of the opa gene family and 11 opa genes have been identified (4,5).…”