The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge

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 prot...

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Autores principales:	Jeremy S. Dyke, Maria Cristina Huertas-Diaz, Frank Michel, Nathan E. Holladay, Robert J. Hogan, Biao He, Eric R. Lafontaine
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	burkholderia mallei glanders virulence mouse aerosol infection vaccine protective antigen Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/5d43650e1d1345b1b0e37283cc442043
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spelling	oai:doaj.org-article:5d43650e1d1345b1b0e37283cc4420432021-11-17T14:21:58ZThe Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge2150-55942150-560810.1080/21505594.2020.1804275https://doaj.org/article/5d43650e1d1345b1b0e37283cc4420432020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1804275https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Burkholderia 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.Jeremy S. DykeMaria Cristina Huertas-DiazFrank MichelNathan E. HolladayRobert J. HoganBiao HeEric R. LafontaineTaylor & Francis Grouparticleburkholderia malleiglandersvirulencemouse aerosol infectionvaccineprotective antigenInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 1024-1040 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	burkholderia mallei glanders virulence mouse aerosol infection vaccine protective antigen Infectious and parasitic diseases RC109-216
spellingShingle	burkholderia mallei glanders virulence mouse aerosol infection vaccine protective antigen Infectious and parasitic diseases RC109-216 Jeremy S. Dyke Maria Cristina Huertas-Diaz Frank Michel Nathan E. Holladay Robert J. Hogan Biao He Eric R. Lafontaine The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge
description	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.
format	article
author	Jeremy S. Dyke Maria Cristina Huertas-Diaz Frank Michel Nathan E. Holladay Robert J. Hogan Biao He Eric R. Lafontaine
author_facet	Jeremy S. Dyke Maria Cristina Huertas-Diaz Frank Michel Nathan E. Holladay Robert J. Hogan Biao He Eric R. Lafontaine
author_sort	Jeremy S. Dyke
title	The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge
title_short	The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge
title_full	The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge
title_fullStr	The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge
title_full_unstemmed	The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge
title_sort	peptidoglycan-associated lipoprotein pal contributes to the virulence of burkholderia mallei and provides protection against lethal aerosol challenge
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/5d43650e1d1345b1b0e37283cc442043
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The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge

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