Mouse Anti-Bordetella pertussis Adenylate Cyclase Toxin (aa 1156-1489) Monoclonal Antibody, clone 3G6

We found and isolated adenylate cyclase toxin (ACT) from Bordetella pertussis culture supernatant that had gone through a logarithmic phase of growth. It converts ATP into cAMP just like bacteria's intracellular adenylate cyclase (AC). ACT can only get inside the phagocytic cells. Once inside, it generates supraphysiological levels of cAMP, which significantly impairs the bactericidal capabilities of these cells. This mechanism aids the bacteria in colonizing the respiratory tract by weakening the host's immune defenses. The fact that the toxin targets and destabilises phagocytes is crucial for B. pertussis infection in the early stages. Through interference with the normal function of these immune cells, ACT permits the bacteria to avoid the host's original immune reaction and thus set up and survive in the lungs.

ACT is encoded by the CyaA gene in Bordetella pertussis and one of the key virulence factors for B. pertussis early colonisation of the respiratory tract during infection. There is an N-terminal calmodulin-dependent adenylate cyclase domain and a C-terminal hemolysin domain of ACT. The full activity of ACT depends on post-translational modification by CyaC, which palmitoylates ACT at lysine residues 860 and 983. ACT gets converted in the bacterial cell by CyaC protein into an active protein that can overwhelm the host's natural defences. It attacks macrophages, DCs, neutrophils and non-phagocytic cells, and causes intracellular cAMP levels to spike. This elevation in cAMP impairs the bactericidal capabilities of phagocytes. Additionally, ACT can act on DCs, increasing their intracellular cAMP concentration. High levels of cAMP in DCs enhance mitogen-activated protein kinase phosphorylation while inhibiting the expression of interferon regulatory factors 1 (IRF-1) and IRF-8. This leads to increased production of IL-10 and suppression of pro-inflammatory factors.

Figure 1. Schematic representation of the CyaA molecule
(Source: Masin J, et al. 2015)

ACT is a virulence factor secreted by Bordetella pertussis that's not just important during the incubation phase of bacteria but can also be a protective antigen. Protective immunogenicity of ACT is also dependent on CyaC-mediated modification of lysine 983 (perhaps because the modified area is associated with an immunodominant epitope or because CyaC-induced modification changes the molecular structure and so allows for immunodominant epitopes). Researchers have engineered ACT to produce a protein lacking adenylate cyclase (AC) activity. When this AC-inactive ACT was combined with acellular pertussis (aP) vaccine and used to immunize mice, it demonstrated optimal adjuvant effects, significantly reducing the number of bacteria colonizing the lungs. This finding suggests that AC-inactive ACT could serve as a novel adjuvant for aP vaccines, showing promising potential for future applications.

Mouse Anti-B. pertussis Adenylate Cyclase Toxin (aa 1156-1489) Monoclonal Antibody
Mouse Anti-B. pertussis ACT (aa 1156-1489) Monoclonal Antibody
Mouse Anti-B. pertussis CyaA (aa 1156-1489) Monoclonal Antibody