Exchange protein directly activated by cAMP plays a critical role in bacterial invasion during fatal rickettsioses.
Proc Natl Acad Sci U S A
; 110(48): 19615-20, 2013 Nov 26.
Article
em En
| MEDLINE
| ID: mdl-24218580
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Infecções por Rickettsia
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Aderência Bacteriana
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Transdução de Sinais
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Fatores de Troca do Nucleotídeo Guanina
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Interações Hospedeiro-Patógeno
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Hidrazonas
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Isoxazóis
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article