Neisseria meningitidis NadA is a new invasin which promotes bacterial adhesion to and penetration into human epithelial cells

Abstract

SummaryNeisseria meningitidis is a human pathogen, which is a major cause of sepsis and meningitis. The bacterium colonizes the upper respiratory tract of approximately 10% of humans where it lives as a commensal. On rare occasions, it crosses the epithelium and reaches the bloodstream causing sepsis. From the bloodstream it translocates the blood-brain barrier, causing meningitis. Although all strains have the potential to cause disease, a subset of them, which belongs to hypervirulent lineages, causes disease more frequently than others. Recently, we described NadA, a novel antigen of N. meningitidis , present in three of the four known hypervirulent lineages. Here we show that NadA is a novel bacterial invasin which, when expressed on the surface of Escherichia coli , promotes adhesion to and invasion into Chang epithelial cells. Deletion of the N-terminal globular domain of recombinant NadA or pronase treatment of human cells abrogated the adhesive phenotype. A hypervirulent strain of N. meningitidis where the nadA gene was inactivated had a reduced ability to adhere to and invade into epithelial cells in vitro . NadA is likely to improve the fitness of N. meningitidis contributing to the increased virulence of strains that belong to the hypervirulent lineages.

Neisseria meningitidis Adhesin NadA Targets β1 Integrins

“…However, we could demonstrate that NadA as well as YadA mediate adhesion to Chang cells and triggering of internalization by using a pYVand inv deleted Y. enterocolitica mutant. These latter results are in agreement with experiments using E. coli expressing nadA, as previously shown (13). Moraxella catarrhalis Oca family member UspA1 and Neisseria Opa proteins are known to be recognized by CEACAMs, which are expressed by diverse host cells (34).…”

“…NadA-specific Cell Adhesion and Invasion Is Not Detectable in N. meningitidis-NadA has previously been described as an invasin, mediating invasion of nadA-expressing E. coli and meningococci into human Chang cells (13). To test whether ␤1 integrins are involved in mediating adhesion and invasion of N. meningitidis we used the unencapsulated N. meningitidis strain MC58 ⌬siaD and the isogenic nadA mutant MC58 ⌬siaD ⌬nadA for cellular infection of GE-11-␤1 and GE-11 cell monolayers for 3 h (moi 100).…”

“…it has been demonstrated that NadA produced by N. meningitidis or E. coli does not bind to ECM proteins (13). Therefore we investigated the ability of full-length NadA produced on the surface of Y. enterocolitica to mediate interaction with immobilized collagen type I, fibronectin, and matrigel, respectively, using an ELISA technique (22).…”

“…Whereas YadA of enteropathogenic Yersinia species mediates binding to diverse ECM proteins (9 -12), epithelial cells, and neutrophils, NadA of N. meningitidis does not bind to ECM proteins but binds to a restricted number of cell types such as Chang cells, HEp-2 or human monocytes/macrophages but fails to bind to HUVEC endothelial cells or human endometrium cell line Hec-1B (13)(14)(15).…”

HadA is an atypical new multifunctional trimeric coiled-coil adhesin ofHaemophilus influenzaebiogroupaegyptius, which promotes entry into host cells

“…To date, all of them appear to have adhesive activity that is involved in mediating bacterial interaction with either host cells or extracellular matrix (ECM) proteins and in some cases in inducing invasion of target cells (Yang and Isberg, 1993;McMichael et al, 1998;Eitel and Dersch, 2002;Laarmann et al, 2002;Ray et al, 2002;Roggenkamp et al, 2003;Li et al, 2004;Riess et al, 2004;Zhang et al, 2004;Capecchi et al, 2005;Girard and Mourez, 2006;Heise and Dersch, 2006;Scarselli et al, 2006).…”