The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge
| Autor: | Eric R. Lafontaine, Frank Michel, Jeremy S. Dyke, Maria Cristina Huertas-Diaz, Nathan E Holladay, Robert J. Hogan, Biao He |
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| Rok vydání: | 2020 |
| Předmět: |
Infectious and parasitic diseases
RC109-216 Mice chemistry.chemical_compound vaccine protective antigen Organism Mice Inbred BALB C Vaccines Synthetic 0303 health sciences Virulence Zoonosis mouse aerosol infection humanities Infectious Diseases Bacterial Vaccines Female Research Article Research Paper Microbiology (medical) Lipoproteins Genetic Vectors Immunology Peptidoglycan Biology Burkholderia mallei Microbiology Cell Line 03 medical and health sciences medicine Animals 030304 developmental biology Aerosols 030306 microbiology Macrophages Glanders biology.organism_classification medicine.disease glanders Melioidosis Membrane protein chemistry Parainfluenza Virus 5 Immunization Parasitology Bacteria |
| Zdroj: | Virulence article-version (VoR) Version of Record Virulence, Vol 11, Iss 1, Pp 1024-1040 (2020) |
| ISSN: | 2150-5608 2150-5594 |
| DOI: | 10.1080/21505594.2020.1804275 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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