Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidates.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
Aug 2024
Aug 2024
Historique:
received:
03
01
2024
accepted:
29
07
2024
medline:
27
8
2024
pubmed:
26
8
2024
entrez:
26
8
2024
Statut:
epublish
Résumé
Live attenuated vaccines (LAVs) whose virulence would be controlled at the tissue level could be a crucial tool to effectively fight intracellular bacterial pathogens, because they would optimize the induction of protective immune memory while avoiding the long-term persistence of vaccine strains in the host. Rational development of these new LAVs implies developing an exhaustive map of the bacterial virulence genes according to the host organs implicated. We report here the use of transposon sequencing to compare the bacterial genes involved in the multiplication of Brucella melitensis, a major causative agent of brucellosis, in the lungs and spleens of C57BL/6 infected mice. We found 257 and 135 genes predicted to be essential for B. melitensis multiplication in the spleen and lung, respectively, with 87 genes common to both organs. We selected genes whose deletion is predicted to produce moderate or severe attenuation in the spleen, the main known reservoir of Brucella, and compared deletion mutants for these genes for their ability to protect mice against challenge with a virulent strain of B. melitensis. The protective efficacy of a deletion mutant for the plsC gene, implicated in phospholipid biosynthesis, is similar to that of the reference Rev.1 vaccine but with a shorter persistence in the spleen. Our results demonstrate that B. melitensis faces different selective pressures depending on the organ and underscore the effectiveness of functional genome mapping for the design of new safer LAV candidates.
Identifiants
pubmed: 39186777
doi: 10.1371/journal.ppat.1012459
pii: PPATHOGENS-D-24-00016
doi:
Substances chimiques
Brucella Vaccine
0
Vaccines, Attenuated
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1012459Informations de copyright
Copyright: © 2024 Barbieux et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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