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The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge.
Virulence. 2020 12; 11(1):1024-1040.V

Abstract

BURKHOLDERIA MALLEI

is a highly pathogenic bacterium that causes the fatal zoonosis glanders. The organism specifies multiple membrane proteins, which represent prime targets for the development of countermeasures given their location at the host-pathogen interface. We investigated one of these proteins, Pal, and discovered that it is involved in the ability of B. mallei to resist complement-mediated killing and replicate inside host cells in vitro, is expressed in vivo and induces antibodies during the course of infection, and contributes to virulence in a mouse model of aerosol infection. A mutant in the pal gene of the B. mallei wild-type strain ATCC 23344 was found to be especially attenuated, as BALB/c mice challenged with the equivalent of 5,350 LD50 completely cleared infection. Based on these findings, we tested the hypothesis that a vaccine containing the Pal protein elicits protective immunity against aerosol challenge. To achieve this, the pal gene was cloned in the vaccine vector Parainfluenza Virus 5 (PIV5) and mice immunized with the virus were infected with a lethal dose of B. mallei. These experiments revealed that a single dose of PIV5 expressing Pal provided 80% survival over a period of 40 days post-challenge. In contrast, only 10% of mice vaccinated with a PIV5 control virus construct survived infection. Taken together, our data establish that the Peptidoglycan-associated lipoprotein Pal is a critical virulence determinant of B. mallei and effective target for developing a glanders vaccine.

Authors+Show Affiliations

Department of Infectious Diseases, University of Georgia College of Veterinary Medicine , Athens, GA, USA.Department of Infectious Diseases, University of Georgia College of Veterinary Medicine , Athens, GA, USA.Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia College of Veterinary Medicine , Athens, GA, USA.Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia College of Veterinary Medicine , Athens, GA, USA.Department of Infectious Diseases, University of Georgia College of Veterinary Medicine , Athens, GA, USA. Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia College of Veterinary Medicine , Athens, GA, USA.Department of Infectious Diseases, University of Georgia College of Veterinary Medicine , Athens, GA, USA.Department of Infectious Diseases, University of Georgia College of Veterinary Medicine , Athens, GA, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32799724

Citation

Dyke, Jeremy S., et al. "The Peptidoglycan-associated Lipoprotein Pal Contributes to the Virulence of Burkholderia Mallei and Provides Protection Against Lethal Aerosol Challenge." Virulence, vol. 11, no. 1, 2020, pp. 1024-1040.
Dyke JS, Huertas-Diaz MC, Michel F, et al. The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge. Virulence. 2020;11(1):1024-1040.
Dyke, J. S., Huertas-Diaz, M. C., Michel, F., Holladay, N. E., Hogan, R. J., He, B., & Lafontaine, E. R. (2020). The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge. Virulence, 11(1), 1024-1040. https://doi.org/10.1080/21505594.2020.1804275
Dyke JS, et al. The Peptidoglycan-associated Lipoprotein Pal Contributes to the Virulence of Burkholderia Mallei and Provides Protection Against Lethal Aerosol Challenge. Virulence. 2020;11(1):1024-1040. PubMed PMID: 32799724.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge. AU - Dyke,Jeremy S, AU - Huertas-Diaz,Maria Cristina, AU - Michel,Frank, AU - Holladay,Nathan E, AU - Hogan,Robert J, AU - He,Biao, AU - Lafontaine,Eric R, PY - 2020/8/18/entrez PY - 2020/8/18/pubmed PY - 2021/7/20/medline KW - Burkholderia mallei KW - glanders KW - mouse aerosol infection KW - protective antigen KW - vaccine KW - virulence SP - 1024 EP - 1040 JF - Virulence JO - Virulence VL - 11 IS - 1 N2 - BURKHOLDERIA MALLEI: is a highly pathogenic bacterium that causes the fatal zoonosis glanders. The organism specifies multiple membrane proteins, which represent prime targets for the development of countermeasures given their location at the host-pathogen interface. We investigated one of these proteins, Pal, and discovered that it is involved in the ability of B. mallei to resist complement-mediated killing and replicate inside host cells in vitro, is expressed in vivo and induces antibodies during the course of infection, and contributes to virulence in a mouse model of aerosol infection. A mutant in the pal gene of the B. mallei wild-type strain ATCC 23344 was found to be especially attenuated, as BALB/c mice challenged with the equivalent of 5,350 LD50 completely cleared infection. Based on these findings, we tested the hypothesis that a vaccine containing the Pal protein elicits protective immunity against aerosol challenge. To achieve this, the pal gene was cloned in the vaccine vector Parainfluenza Virus 5 (PIV5) and mice immunized with the virus were infected with a lethal dose of B. mallei. These experiments revealed that a single dose of PIV5 expressing Pal provided 80% survival over a period of 40 days post-challenge. In contrast, only 10% of mice vaccinated with a PIV5 control virus construct survived infection. Taken together, our data establish that the Peptidoglycan-associated lipoprotein Pal is a critical virulence determinant of B. mallei and effective target for developing a glanders vaccine. SN - 2150-5608 UR - https://www.unboundmedicine.com/medline/citation/32799724/The_Peptidoglycan_associated_lipoprotein_Pal_contributes_to_the_virulence_of_Burkholderia_mallei_and_provides_protection_against_lethal_aerosol_challenge_ L2 - https://www.tandfonline.com/doi/full/10.1080/21505594.2020.1804275 DB - PRIME DP - Unbound Medicine ER -