Expression of pathogen-like Opa adhesins in commensal Neisseria: genetic and functional analysis.
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.
Toleman
M
M
Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, UK.
Aho
E
E
Virji
M
M
D018829:Adhesins, Bacterial / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D001422:Bacterial Adhesion; D016466:CHO Cells; D015815:Cell Adhesion Molecules; D003001:Cloning, Molecular; D006224:Cricetinae; D016680:Genome, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D009343:Neisseria / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity*; D010802:Phylogeny; D016415:Sequence Alignment; D014162:Transfection
D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; C050308:opacity proteins