Search

Bordetella pertussis is the causal agent of whooping cough (pertussis), a highly contagious respiratory illness. This organism produces a group of virulence factors between which is possible to find to the adenylate cyclase toxin-hemolysin (CyaA) and pertactin (Prn). The first allows the bacteria inhibit phagocytosis and inflammatory response in the host, whereas the second is an adhesin that is frequently included as a component in acellular vaccines against B. pertussis. The objective of this work was to obtain Bordetella pertussis LPA311 mutants lacking adenylate cyclase toxin - hemolysin and largest producers of pertactin 2 with vaccinal purposes. The results revealed that in the seven mutants obtained the cyaA gene has been replaced by the prn2 gene. Additionally, one-way ANOVA showed that the levels of production of Prn in five of the mutants were significantly higher to the levels produced by the control (p < 0.05). These results showed that the strategy of replacement of the gene cyaA by the prn2 gene on B. pertussis LPA311, allows eliminating the CyaA expression and increasing the Prn production. [ABSTRACT FROM AUTHOR]

The adenylate cyclase - hemolysin toxin (ACT) is one of the main virulence factors in Bordetella pertussis. It was discovered in 1973 by Wolff and Cook as a contaminant in vaccine formulations against this microorganism. It belongs to the family of toxins that form pores at the plasma membrane of target cells and reaches the highest expression during the virulent phase of the bacteria. This toxin has 1706 aminoacid residues and is composed of two domains: the N-terminal domain, with calmodulin-sensitive adenylate cyclase activity and the C-terminal domain that promotes the formation of pores at the membrane of target cells. Furthermore, the integrins type αMβ2 molecules are natural receptors for the toxin, which binds to the N-glycosylated extracellular portion. ACT allows the bacteria to inhibit phagocytosis, activation of type 1 T-helper cells and cytotoxic T cells as well as gamma interferon production by macrophages. Despite of its toxic effects, the inactivated form of the toxin has been used in delivering immunogenic epitopes to antigen-presenting cells, in the identification of proteins secreted by the type III secretion system and in protein-protein interactions studies. [ABSTRACT FROM AUTHOR]