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Antibodies against In Vivo-Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei.
Infect Immun. 2017 08; 85(8)II

Abstract

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.

Authors+Show Affiliations

Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA. Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.Department of Infectious Diseases, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA jhogan@uga.edu. Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, College of Veterinary Medicine, Athens, Georgia, USA.

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

28507073

Citation

Zimmerman, Shawn M., et al. "Antibodies Against in Vivo-Expressed Antigens Are Sufficient to Protect Against Lethal Aerosol Infection With Burkholderia Mallei and Burkholderia Pseudomallei." Infection and Immunity, vol. 85, no. 8, 2017.
Zimmerman SM, Dyke JS, Jelesijevic TP, et al. Antibodies against In Vivo-Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei. Infect Immun. 2017;85(8).
Zimmerman, S. M., Dyke, J. S., Jelesijevic, T. P., Michel, F., Lafontaine, E. R., & Hogan, R. J. (2017). Antibodies against In Vivo-Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei. Infection and Immunity, 85(8). https://doi.org/10.1128/IAI.00102-17
Zimmerman SM, et al. Antibodies Against in Vivo-Expressed Antigens Are Sufficient to Protect Against Lethal Aerosol Infection With Burkholderia Mallei and Burkholderia Pseudomallei. Infect Immun. 2017;85(8) PubMed PMID: 28507073.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antibodies against In Vivo-Expressed Antigens Are Sufficient To Protect against Lethal Aerosol Infection with Burkholderia mallei and Burkholderia pseudomallei. AU - Zimmerman,Shawn M, AU - Dyke,Jeremy S, AU - Jelesijevic,Tomislav P, AU - Michel,Frank, AU - Lafontaine,Eric R, AU - Hogan,Robert J, Y1 - 2017/07/19/ PY - 2017/02/12/received PY - 2017/05/08/accepted PY - 2017/5/17/pubmed PY - 2017/8/8/medline PY - 2017/5/17/entrez KW - aerosols KW - autotransporter proteins KW - biodefense KW - countermeasures KW - glanders KW - immunoprotective antibodies KW - melioidosis KW - virulence determinants JF - Infection and immunity JO - Infect Immun VL - 85 IS - 8 N2 - 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. SN - 1098-5522 UR - https://www.unboundmedicine.com/medline/citation/28507073/Antibodies_against_In_Vivo_Expressed_Antigens_Are_Sufficient_To_Protect_against_Lethal_Aerosol_Infection_with_Burkholderia_mallei_and_Burkholderia_pseudomallei_ L2 - http://iai.asm.org/cgi/pmidlookup?view=long&pmid=28507073 DB - PRIME DP - Unbound Medicine ER -