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Bacterial effector binds host cell adenylyl cyclase to potentiate Gαs-dependent cAMP production
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 1211770
Author(s) Pulliainen, A. T.; Pieles, K.; Brand, C. S.; Hauert, B.; Böhm, A.; Quebatte, M.; Wepf, A.; Gstaiger, M.; Aebersold, R.; Dessauer, C. W.; Dehio, C.
Author(s) at UniBasel Dehio, Christoph
Québatte, Maxime
Böhm, Alexander Stephan
Year 2012
Title Bacterial effector binds host cell adenylyl cyclase to potentiate Gαs-dependent cAMP production
Journal Proceedings of the National Academy of Sciences of the United States of America
Volume 109
Number 24
Pages / Article-Number 9581-6
Keywords bacterial infection, apoptosis, tumorigenesis, type IV secretion
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 α-subunit of the AC-stimulating G protein (Gαs) 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 Gαs and BepA in Escherichia coli; (ii) in vitro AC assays with membrane-anchored full-length human AC and recombinant BepA and Gαs; (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 Gαs-dependent cAMP production. As opposed to the known microbial mechanisms, such as ADP ribosylation of G protein α-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 Gαs. We propose that this mechanism contributes to the persistence of Bartonella henselae in the chronically infected vascular endothelium.

Publisher National Academy of Sciences
ISSN/ISBN 0027-8424 ; 1091-6490
edoc-URL http://edoc.unibas.ch/dok/A6008364
Full Text on edoc Restricted
Digital Object Identifier DOI 10.1073/pnas.1117651109
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/22635269
ISI-Number WOS:000305511300075
Document type (ISI) Journal Article
 
   

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