Cholera toxin and extracellular Ca2+ induce adherence of non-piliated Neisseria: Evidence for an important role of G-proteins and Rho in the bacteria-cell interaction

Abstract

In this study, we characterize the interaction between non-piliated (P) Neisseria gonorrhoeae and human epithelial cells. P- mutants lacking the pilus subunit protein PilE attach at low levels to cells. Although the binding may not lead to heavy inflammatory responses, the interaction between P Neisseria and host cells most probably play a role in colonization and asymptomatic carriage of the pathogen. Here we show that the adherence of P- N. gonorrhoeae is blocked by GDP-β-S [guanosine 5'-O-(thio)diphosphate], a non-hydrolyzable GTP analogue, and by C3 exotoxin, an inhibitor of the small G-protein Rho. G-protein activators such as cholera toxin, that activates G(s), and fluoroaluminate, a general G-protein activator, induced bacterial adherence. Furthermore, increase of the extracellular free [Ca2+] dramatically enhanced adherence of non-piliated Neisseria. The pharynx and the urogenital tract are natural entry sites of the pathogenic Neisseria species, and at both sites the epithelial cells can be exposed to wide variations in Ca2+' concentration. Taken together, these data show the importance of extracellular Ca2+ in the pathogenic Neisseria-host interaction, and reveal a novel function of cholera toxin, namely induction of bacterial adherence.