Integrity of the C-terminal hemolysin domain is required for protective activity of the Bordetella pertussis adenylate cyclase hemolysin
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文摘
Bordetella pertussis adenylate cyclase hemolysin (AC-Hly), encoded by the cyaA gene, belongs to the RTX family of toxins which possess extensive glycine-rich repeats in their carboxy-terminal portion. AC-Hly possesses both an adenylate cyclase N-terminal domain and a hemolytic C-terminal domain. B. pertussis AC-Hly is a protective antigen against bacterial colonization of the mouse respiratory tract by B. pertussis. Using different deletion mutants of the recombinant AC-Hly, we showed that the last 217 aminoacids, containing secretion signal, are necessary for the protective activity of AC-Hly. However, the last 217 residues of AC-Hly are not sufficient to form a distinct protective epitope per se; integrity of the whole domain containing the last 800 residues is required. The N-terminal AC domain is devoid of protective activity. AC-Hly from B. bronchiseptica, the animal pathogen, is also a protective antigen against B. bronchiseptica infection. However, no cross-immunity exists betweenB. pertussis and B. bronchiseptica AC-Hlys. We have cloned and sequenced the B. bronchiseptica cyaA gene and showed that the differences between the B. pertussis and the B. bronchiseptica AC-Hlys are mainly located at residues in the C-terminal part of the molecule, which contains the glycine-rich repeats. We therefore suggest that this part of the molecule, which is possibly surface accessible and antigenically variable, is most important for protective activity.