cAMP signalling of Bordetella adenylate cyclase toxin through the SHP-1 phosphatase activates the BimEL-Bax pro-apoptotic cascade in phagocytes

0462060 - MBÚ 2017 RIV US eng J - Journal Article
Ahmad, Jawid Nazir - Černý, Ondřej - Linhartová, Irena - Mašín, Jiří - Osička, Radim - Šebo, Peter
cAMP signalling of Bordetella adenylate cyclase toxin through the SHP-1 phosphatase activates the BimEL-Bax pro-apoptotic cascade in phagocytes.
Cellular Microbiology. Roč. 18, č. 3 (2016), s. 384-398. ISSN 1462-5814. E-ISSN 1462-5822
R&D Projects: GA ČR GA13-14547S; GA ČR(CZ) GAP302/11/0580; GA ČR GAP302/12/0460
Institutional support: RVO:61388971
Keywords : FORKHEAD TRANSCRIPTION FACTOR * HUMAN T-CELLS * DENDRITIC CELLS
Subject RIV: EE - Microbiology, Virology
Impact factor: 4.554, year: 2016

The adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) plays a key role in virulence of Bordetella pertussis. CyaA penetrates myeloid cells expressing the complement receptor 3 ((M2) integrin CD11b/CD18) and subverts bactericidal capacities of neutrophils and macrophages by catalysing unregulated conversion of cytosolic ATP to the key signalling molecule adenosine 3',5'-cyclic monophosphate (cAMP). We show that the signalling of CyaA-produced cAMP hijacks, by an as yet unknown mechanism, the activity of the tyrosine phosphatase SHP-1 and activates the pro-apoptotic BimEL-Bax cascade. Mitochondrial hyperpolarization occurred in human THP-1 macrophages within 10min of exposure to low CyaA concentrations (e.g. 20ngml(-1)) and was accompanied by accumulation of BimEL and association of the pro-apoptotic factor Bax with mitochondria.
Permanent Link: http://hdl.handle.net/11104/0261603