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Antibodies against In Vivo-Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei.
Zimmerman, Shawn M; Dyke, Jeremy S; Jelesijevic, Tomislav P; Michel, Frank; Lafontaine, Eric R; Hogan, Robert J.
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  • Zimmerman SM; Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.
  • Dyke JS; Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.
  • Jelesijevic TP; Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.
  • Michel F; Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.
  • Lafontaine ER; Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.
  • Hogan RJ; Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.
Infect Immun ; 85(8)2017 08.
Article en En | MEDLINE | ID: mdl-28507073
Burkholderia mallei, a facultative intracellular bacterium and tier 1 biothreat, causes the fatal zoonotic disease glanders. The organism possesses multiple genes encoding autotransporter proteins, which represent important virulence factors and targets for developing countermeasures in pathogenic Gram-negative bacteria. In the present study, we investigated one of these autotransporters, BatA, and demonstrate that it displays lipolytic activity, aids in intracellular survival, is expressed in vivo, elicits production of antibodies during infection, and contributes to pathogenicity in a mouse aerosol challenge model. A mutation in the batA gene of wild-type strain ATCC 23344 was found to be particularly attenuating, as BALB/c mice infected with the equivalent of 80 median lethal doses cleared the organism. This finding prompted us to test the hypothesis that vaccination with the batA mutant strain elicits protective immunity against subsequent infection with wild-type bacteria. We discovered that not only does vaccination provide high levels of protection against lethal aerosol challenge with B. mallei ATCC 23344, it also protects against infection with multiple isolates of the closely related organism and causative agent of melioidosis, Burkholderia pseudomallei Passive-transfer experiments also revealed that the protective immunity afforded by vaccination with the batA mutant strain is predominantly mediated by IgG antibodies binding to antigens expressed exclusively in vivo Collectively, our data demonstrate that BatA is a target for developing medical countermeasures and that vaccination with a mutant lacking expression of the protein provides a platform to gain insights regarding mechanisms of protective immunity against B. mallei and B. pseudomallei, including antigen discovery.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Burkholderia pseudomallei / Burkholderia mallei / Melioidosis / Anticuerpos Antibacterianos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Infect Immun Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Burkholderia pseudomallei / Burkholderia mallei / Melioidosis / Anticuerpos Antibacterianos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Infect Immun Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos