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

0482215 - MBÚ 2018 RIV CH eng J - Journal Article
Novák, Jakub - Černý, Ondřej - Osičková, Adriana - Linhartová, Irena - Mašín, Jiří - Bumba, Ladislav - Šebo, Peter - Osička, Radim
Structure-Function Relationships Underlying the Capacity of Bordetella Adenylate Cyclase Toxin to Disarm Host Phagocytes.
Toxins. Roč. 9, č. 10 (2017), s. 1-28, č. článku 300. ISSN 2072-6651. E-ISSN 2072-6651
R&D Projects: GA ČR GA15-09157S; GA ČR(CZ) GA16-05919S; GA MŠMT(CZ) LM2015064; GA MZd(CZ) NV16-28126A
Institutional support: RVO:61388971
Keywords : adenylate cyclase toxin * Bordetella * cAMP
OECD category: Microbiology
Impact factor: 3.273, year: 2017

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 ((M2)) 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.
Permanent Link: http://hdl.handle.net/11104/0277606