Characterization of Inner and Outer Membrane Proteins from <italic toggle="yes">Francisella tularensis</italic> Strains LVS and Schu S4 and Identification of Potential Subunit Vaccine Candidates

ABSTRACT Francisella tularensis is the causative agent of tularemia and a potential bioterrorism agent. In the present study, we isolated, identified, and quantified the proteins present in the membranes of the virulent type A strain, Schu S4, and the attenuated type B strain, LVS (live vaccine stra...

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Autores principales:	Deborah M. B. Post, Bram Slütter, Birgit Schilling, Aroon T. Chande, Jed A. Rasmussen, Bradley D. Jones, Alexandria K. D’Souza, Lorri M. Reinders, John T. Harty, Bradford W. Gibson, Michael A. Apicella
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Franscisella tularensis immunity inner membrane proteins outer membrane proteins proteomics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/10b004effe754b49ba49b22ca128ad0f
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spelling	oai:doaj.org-article:10b004effe754b49ba49b22ca128ad0f2021-11-15T15:51:51ZCharacterization of Inner and Outer Membrane Proteins from <italic toggle="yes">Francisella tularensis</italic> Strains LVS and Schu S4 and Identification of Potential Subunit Vaccine Candidates10.1128/mBio.01592-172150-7511https://doaj.org/article/10b004effe754b49ba49b22ca128ad0f2017-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01592-17https://doaj.org/toc/2150-7511ABSTRACT Francisella tularensis is the causative agent of tularemia and a potential bioterrorism agent. In the present study, we isolated, identified, and quantified the proteins present in the membranes of the virulent type A strain, Schu S4, and the attenuated type B strain, LVS (live vaccine strain). Spectral counting of mass spectrometric data showed enrichment for membrane proteins in both strains. Mice vaccinated with whole LVS membranes encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing the adjuvant polyinosinic-polycytidylic acid [poly(I·C)] showed significant protection against a challenge with LVS compared to the results seen with naive mice or mice vaccinated with either membranes or poly(I·C) alone. The PLGA-encapsulated Schu S4 membranes with poly(I·C) alone did not significantly protect mice from a lethal intraperitoneal challenge with Schu S4; however, this vaccination strategy provided protection from LVS challenge. Mice that received the encapsulated Schu S4 membranes followed by a booster of LVS bacteria showed significant protection with respect to a lethal Schu S4 challenge compared to control mice. Western blot analyses of the sera from the Schu S4-vaccinated mice that received an LVS booster showed four immunoreactive bands. One of these bands from the corresponding one-dimensional (1D) SDS-PAGE experiment represented capsule. The remaining bands were excised, digested with trypsin, and analyzed using mass spectrometry. The most abundant proteins present in these immunoreactive samples were an outer membrane OmpA-like protein, FopA; the type IV pilus fiber building block protein; a hypothetical membrane protein; and lipoproteins LpnA and Lpp3. These proteins should serve as potential targets for future recombinant protein vaccination studies. IMPORTANCE The low infectious dose, the high potential mortality/morbidity rates, and the ability to be disseminated as an aerosol make Francisella tularensis a potential agent for bioterrorism. These characteristics led the Centers for Disease Control (CDC) to classify F. tularensis as a Tier 1 pathogen. Currently, there is no vaccine approved for general use in the United States.Deborah M. B. PostBram SlütterBirgit SchillingAroon T. ChandeJed A. RasmussenBradley D. JonesAlexandria K. D’SouzaLorri M. ReindersJohn T. HartyBradford W. GibsonMichael A. ApicellaAmerican Society for MicrobiologyarticleFranscisella tularensisimmunityinner membrane proteinsouter membrane proteinsproteomicsMicrobiologyQR1-502ENmBio, Vol 8, Iss 5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Franscisella tularensis immunity inner membrane proteins outer membrane proteins proteomics Microbiology QR1-502
spellingShingle	Franscisella tularensis immunity inner membrane proteins outer membrane proteins proteomics Microbiology QR1-502 Deborah M. B. Post Bram Slütter Birgit Schilling Aroon T. Chande Jed A. Rasmussen Bradley D. Jones Alexandria K. D’Souza Lorri M. Reinders John T. Harty Bradford W. Gibson Michael A. Apicella Characterization of Inner and Outer Membrane Proteins from <italic toggle="yes">Francisella tularensis</italic> Strains LVS and Schu S4 and Identification of Potential Subunit Vaccine Candidates
description	ABSTRACT Francisella tularensis is the causative agent of tularemia and a potential bioterrorism agent. In the present study, we isolated, identified, and quantified the proteins present in the membranes of the virulent type A strain, Schu S4, and the attenuated type B strain, LVS (live vaccine strain). Spectral counting of mass spectrometric data showed enrichment for membrane proteins in both strains. Mice vaccinated with whole LVS membranes encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing the adjuvant polyinosinic-polycytidylic acid [poly(I·C)] showed significant protection against a challenge with LVS compared to the results seen with naive mice or mice vaccinated with either membranes or poly(I·C) alone. The PLGA-encapsulated Schu S4 membranes with poly(I·C) alone did not significantly protect mice from a lethal intraperitoneal challenge with Schu S4; however, this vaccination strategy provided protection from LVS challenge. Mice that received the encapsulated Schu S4 membranes followed by a booster of LVS bacteria showed significant protection with respect to a lethal Schu S4 challenge compared to control mice. Western blot analyses of the sera from the Schu S4-vaccinated mice that received an LVS booster showed four immunoreactive bands. One of these bands from the corresponding one-dimensional (1D) SDS-PAGE experiment represented capsule. The remaining bands were excised, digested with trypsin, and analyzed using mass spectrometry. The most abundant proteins present in these immunoreactive samples were an outer membrane OmpA-like protein, FopA; the type IV pilus fiber building block protein; a hypothetical membrane protein; and lipoproteins LpnA and Lpp3. These proteins should serve as potential targets for future recombinant protein vaccination studies. IMPORTANCE The low infectious dose, the high potential mortality/morbidity rates, and the ability to be disseminated as an aerosol make Francisella tularensis a potential agent for bioterrorism. These characteristics led the Centers for Disease Control (CDC) to classify F. tularensis as a Tier 1 pathogen. Currently, there is no vaccine approved for general use in the United States.
format	article
author	Deborah M. B. Post Bram Slütter Birgit Schilling Aroon T. Chande Jed A. Rasmussen Bradley D. Jones Alexandria K. D’Souza Lorri M. Reinders John T. Harty Bradford W. Gibson Michael A. Apicella
author_facet	Deborah M. B. Post Bram Slütter Birgit Schilling Aroon T. Chande Jed A. Rasmussen Bradley D. Jones Alexandria K. D’Souza Lorri M. Reinders John T. Harty Bradford W. Gibson Michael A. Apicella
author_sort	Deborah M. B. Post
title	Characterization of Inner and Outer Membrane Proteins from <italic toggle="yes">Francisella tularensis</italic> Strains LVS and Schu S4 and Identification of Potential Subunit Vaccine Candidates
title_short	Characterization of Inner and Outer Membrane Proteins from <italic toggle="yes">Francisella tularensis</italic> Strains LVS and Schu S4 and Identification of Potential Subunit Vaccine Candidates
title_full	Characterization of Inner and Outer Membrane Proteins from <italic toggle="yes">Francisella tularensis</italic> Strains LVS and Schu S4 and Identification of Potential Subunit Vaccine Candidates
title_fullStr	Characterization of Inner and Outer Membrane Proteins from <italic toggle="yes">Francisella tularensis</italic> Strains LVS and Schu S4 and Identification of Potential Subunit Vaccine Candidates
title_full_unstemmed	Characterization of Inner and Outer Membrane Proteins from <italic toggle="yes">Francisella tularensis</italic> Strains LVS and Schu S4 and Identification of Potential Subunit Vaccine Candidates
title_sort	characterization of inner and outer membrane proteins from <italic toggle="yes">francisella tularensis</italic> strains lvs and schu s4 and identification of potential subunit vaccine candidates
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/10b004effe754b49ba49b22ca128ad0f
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Characterization of Inner and Outer Membrane Proteins from <italic toggle="yes">Francisella tularensis</italic> Strains LVS and Schu S4 and Identification of Potential Subunit Vaccine Candidates

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