Structure–Function Relationships Underlying the Capacity of Bordetella Adenylate Cyclase Toxin to Disarm Host Phagocytes

Toxins

Adriana Osickova¹  Ladislav Bumba¹  Peter Sebo¹  Irena Linhartova¹  Radim Osicka¹  Ondrej Cerny¹  Jakub Novak¹  Jiri Masin¹ 

[1] Institute of Microbiology of the CAS, v.v.i., 142 20 Prague, Czech Republic;

关键词: adenylate cyclase toxin;    Bordetella;    β2 integrins;    cAMP;    CD11b/CD18;    cell signaling;    complement receptor 3;    innate immunity;    membrane pores;    repeats-in-toxin;   

DOI  :  10.3390/toxins9100300

来源: DOAJ

【 摘 要 】

Bordetellae, pathogenic to mammals, produce an immunomodulatory adenylate cyclase toxin–hemolysin (CyaA, ACT or AC-Hly) that enables them to overcome the innate immune defense of the host. CyaA subverts host phagocytic cells by an orchestrated action of its functional domains, where an extremely catalytically active adenylyl cyclase enzyme is delivered into phagocyte cytosol by a pore-forming repeat-in-toxin (RTX) cytolysin moiety. By targeting sentinel cells expressing the complement receptor 3, known as the CD11b/CD18 (αMβ2) integrin, CyaA compromises the bactericidal functions of host phagocytes and supports infection of host airways by Bordetellae. Here, we review the state of knowledge on structural and functional aspects of CyaA toxin action, placing particular emphasis on signaling mechanisms by which the toxin-produced 3′,5′-cyclic adenosine monophosphate (cAMP) subverts the physiology of phagocytic cells.

【 授权许可】

Unknown