Exchange protein directly activated by cAMP plays a critical role in bacterial invasion during fatal rickettsioses.

Abstract:

:Rickettsiae are responsible for some of the most devastating human infections. A high infectivity and severe illness after inhalation make some rickettsiae bioterrorism threats. We report that deletion of the exchange protein directly activated by cAMP (Epac) gene, Epac1, in mice protects them from an ordinarily lethal dose of rickettsiae. Inhibition of Epac1 suppresses bacterial adhesion and invasion. Most importantly, pharmacological inhibition of Epac1 in vivo using an Epac-specific small-molecule inhibitor, ESI-09, completely recapitulates the Epac1 knockout phenotype. ESI-09 treatment dramatically decreases the morbidity and mortality associated with fatal spotted fever rickettsiosis. Our results demonstrate that Epac1-mediated signaling represents a mechanism for host-pathogen interactions and that Epac1 is a potential target for the prevention and treatment of fatal rickettsioses.

authors

Gong B,Shelite T,Mei FC,Ha T,Hu Y,Xu G,Chang Q,Wakamiya M,Ksiazek TG,Boor PJ,Bouyer DH,Popov VL,Chen J,Walker DH,Cheng X

doi

10.1073/pnas.1314400110

subject

Has Abstract

pub_date

2013-11-26 00:00:00

pages

19615-20

issue

48

eissn

0027-8424

issn

1091-6490

pii

1314400110

journal_volume

110

pub_type

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