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.
journal_name
Proc Natl Acad Sci U S Aauthors
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 Xdoi
10.1073/pnas.1314400110subject
Has Abstractpub_date
2013-11-26 00:00:00pages
19615-20issue
48eissn
0027-8424issn
1091-6490pii
1314400110journal_volume
110pub_type
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