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

Cellular Microbiology
Jawid Nazir AhmadPeter Sebo

Abstract

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 (αM β2 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 10 min of exposure to low CyaA concentrations (e.g. 20 ng ml(-1) ) and was accompanied by accumulation of BimEL and association of the pro-apoptotic factor Bax with mitochondria. BimEL accumulation required cAMP/protein kinase A signalling, depended on SHP-1 activity and was selectively inhibited upon small interfering RNA knockdown of SHP-1 but not of the SHP-2 phosphatase. Moreover, signalling of CyaA-produced cAMP inhibited the AKT/protein kinase B pro-survival cascade, enhancing activity of the FoxO3a transcription factor and inducing Bim transcription. Synergy of ...Continue Reading

References

Feb 15, 1986·The Biochemical Journal·M TorruellaH N Torres
Dec 1, 1995·FEMS Microbiology Letters·N Khelef, N Guiso
Sep 18, 1997·The Journal of Infectious Diseases·J S BoschwitzD A Relman
Nov 14, 1997·The Journal of Experimental Medicine·C C DelibriasD T Fearon
Aug 26, 1998·Infection and Immunity·J KorostoffE T Lally
Nov 5, 1999·Annual Review of Microbiology·Y Weinrauch, A Zychlinsky
Sep 22, 2000·The Biochemical Journal·S P DaviesP Cohen
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J G SathishR J Matthews
Jun 22, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·B J ShenkerD R Demuth
Oct 5, 2001·Nature Reviews. Molecular Cell Biology·M P Scheid, J R Woodgett
Feb 1, 2002·FEMS Immunology and Medical Microbiology·Maria BacheletBarbara S Polla
Oct 7, 2003·The Journal of Biological Chemistry·Andrew SuntersEric W-F Lam
Feb 22, 2005·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Devki Nandan, Neil E Reiner
Jan 13, 2006·Current Opinion in Microbiology·Jana VojtovaPeter Sebo
Dec 22, 2007·Nature Reviews. Molecular Cell Biology·Richard J Youle, Andreas Strasser
May 24, 2008·Molecular Cell·Anette HübnerRoger J Davis
Jun 19, 2008·Genes & Development·Der-Fen SuenRichard J Youle
Oct 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jana KamanovaPeter Sebo
Oct 25, 2008·Nature·Evripidis GavathiotisLoren D Walensky

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Citations

Feb 13, 2016·Frontiers in Microbiology·Ana do ValeSandra Sousa
Jan 1, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ondrej CernyPeter Sebo
May 29, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Camille LochtFrançoise Mascart
Oct 6, 2020·Frontiers in Immunology·Jawid Nazir Ahmad, Peter Sebo
Apr 27, 2021·Current Opinion in Infectious Diseases·Jawid Nazir Ahmad, Peter Sebo

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