Identification of the essential Brucella melitensis porin Omp2b as a suppressor of Bax-induced cell death in yeast in a genome-wide screening.

<h4>Background</h4>Inhibition of apoptosis is one of the mechanisms selected by numerous intracellular pathogenic bacteria to control their host cell. Brucellae, which are the causative agent of a worldwide zoonosis, prevent apoptosis of infected cells, probably to support survival of th...

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Main Authors: Géraldine Laloux, Michaël Deghelt, Marie de Barsy, Jean-Jacques Letesson, Xavier De Bolle
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-10-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20949000/pdf/?tool=EBI
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author Géraldine Laloux
Michaël Deghelt
Marie de Barsy
Jean-Jacques Letesson
Xavier De Bolle
author_facet Géraldine Laloux
Michaël Deghelt
Marie de Barsy
Jean-Jacques Letesson
Xavier De Bolle
author_sort Géraldine Laloux
collection DOAJ
description <h4>Background</h4>Inhibition of apoptosis is one of the mechanisms selected by numerous intracellular pathogenic bacteria to control their host cell. Brucellae, which are the causative agent of a worldwide zoonosis, prevent apoptosis of infected cells, probably to support survival of their replication niche.<h4>Methodology/principal findings</h4>In order to identify Brucella melitensis anti-apoptotic effector candidates, we performed a genome-wide functional screening in yeast. The B. melitensis ORFeome was screened to identify inhibitors of Bax-induced cell death in S. cerevisiae. B. melitensis porin Omp2b, here shown to be essential, prevents Bax lethal effect in yeast, unlike its close paralog Omp2a. Our results based on Omp2b size variants characterization suggest that signal peptide processing is required for Omp2b effect in yeast.<h4>Conclusion/significance</h4>We report here the first application to a bacterial genome-wide library of coding sequences of this "yeast-rescue" screening strategy, previously used to highlight several new apoptosis regulators. Our work provides B. melitensis proteins that are candidates for an anti-apoptotic function, and can be tested in mammalian cells in the future. Hypotheses on possible molecular mechanisms of Bax inhibition by the B. melitensis porin Omp2b are discussed.
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spelling doaj.art-3935be1d220446fd9333e573f7e902e32022-12-21T20:34:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-10-01510e1327410.1371/journal.pone.0013274Identification of the essential Brucella melitensis porin Omp2b as a suppressor of Bax-induced cell death in yeast in a genome-wide screening.Géraldine LalouxMichaël DegheltMarie de BarsyJean-Jacques LetessonXavier De Bolle<h4>Background</h4>Inhibition of apoptosis is one of the mechanisms selected by numerous intracellular pathogenic bacteria to control their host cell. Brucellae, which are the causative agent of a worldwide zoonosis, prevent apoptosis of infected cells, probably to support survival of their replication niche.<h4>Methodology/principal findings</h4>In order to identify Brucella melitensis anti-apoptotic effector candidates, we performed a genome-wide functional screening in yeast. The B. melitensis ORFeome was screened to identify inhibitors of Bax-induced cell death in S. cerevisiae. B. melitensis porin Omp2b, here shown to be essential, prevents Bax lethal effect in yeast, unlike its close paralog Omp2a. Our results based on Omp2b size variants characterization suggest that signal peptide processing is required for Omp2b effect in yeast.<h4>Conclusion/significance</h4>We report here the first application to a bacterial genome-wide library of coding sequences of this "yeast-rescue" screening strategy, previously used to highlight several new apoptosis regulators. Our work provides B. melitensis proteins that are candidates for an anti-apoptotic function, and can be tested in mammalian cells in the future. Hypotheses on possible molecular mechanisms of Bax inhibition by the B. melitensis porin Omp2b are discussed.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20949000/pdf/?tool=EBI
spellingShingle Géraldine Laloux
Michaël Deghelt
Marie de Barsy
Jean-Jacques Letesson
Xavier De Bolle
Identification of the essential Brucella melitensis porin Omp2b as a suppressor of Bax-induced cell death in yeast in a genome-wide screening.
PLoS ONE
title Identification of the essential Brucella melitensis porin Omp2b as a suppressor of Bax-induced cell death in yeast in a genome-wide screening.
title_full Identification of the essential Brucella melitensis porin Omp2b as a suppressor of Bax-induced cell death in yeast in a genome-wide screening.
title_fullStr Identification of the essential Brucella melitensis porin Omp2b as a suppressor of Bax-induced cell death in yeast in a genome-wide screening.
title_full_unstemmed Identification of the essential Brucella melitensis porin Omp2b as a suppressor of Bax-induced cell death in yeast in a genome-wide screening.
title_short Identification of the essential Brucella melitensis porin Omp2b as a suppressor of Bax-induced cell death in yeast in a genome-wide screening.
title_sort identification of the essential brucella melitensis porin omp2b as a suppressor of bax induced cell death in yeast in a genome wide screening
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20949000/pdf/?tool=EBI
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