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Bacterial effector binds host cell adenylyl cyclase to potentiate G?s-dependent cAMP production.


ABSTRACT: Subversion of host organism cAMP signaling is an efficient and widespread mechanism of microbial pathogenesis. Bartonella effector protein A (BepA) of vasculotumorigenic Bartonella henselae protects the infected human endothelial cells against apoptotic stimuli by elevation of cellular cAMP levels by an as yet unknown mechanism. Here, adenylyl cyclase (AC) and the ?-subunit of the AC-stimulating G protein (G?s) were identified as potential cellular target proteins for BepA by gel-free proteomics. Results of the proteomics screen were evaluated for physical and functional interaction by: (i) a heterologous in vivo coexpression system, where human AC activity was reconstituted under the regulation of G?s and BepA in Escherichia coli; (ii) in vitro AC assays with membrane-anchored full-length human AC and recombinant BepA and G?s; (iii) surface plasmon resonance experiments; and (iv) an in vivo fluorescence bimolecular complementation-analysis. The data demonstrate that BepA directly binds host cell AC to potentiate the G?s-dependent cAMP production. As opposed to the known microbial mechanisms, such as ADP ribosylation of G protein ?-subunits by cholera and pertussis toxins, the fundamentally different BepA-mediated elevation of host cell cAMP concentration appears subtle and is dependent on the stimulus of a G protein-coupled receptor-released G?s. We propose that this mechanism contributes to the persistence of Bartonella henselae in the chronically infected vascular endothelium.

SUBMITTER: Pulliainen AT 

PROVIDER: S-EPMC3386119 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Bacterial effector binds host cell adenylyl cyclase to potentiate Gαs-dependent cAMP production.

Pulliainen Arto T AT   Pieles Kathrin K   Brand Cameron S CS   Hauert Barbara B   Böhm Alex A   Quebatte Maxime M   Wepf Alexander A   Gstaiger Matthias M   Aebersold Ruedi R   Dessauer Carmen W CW   Dehio Christoph C  

Proceedings of the National Academy of Sciences of the United States of America 20120525 24


Subversion of host organism cAMP signaling is an efficient and widespread mechanism of microbial pathogenesis. Bartonella effector protein A (BepA) of vasculotumorigenic Bartonella henselae protects the infected human endothelial cells against apoptotic stimuli by elevation of cellular cAMP levels by an as yet unknown mechanism. Here, adenylyl cyclase (AC) and the α-subunit of the AC-stimulating G protein (Gαs) were identified as potential cellular target proteins for BepA by gel-free proteomics  ...[more]

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