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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 <jats:italic>Brucella melitensis<\/jats:italic>, 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 <jats:italic>B<\/jats:italic>. <jats:italic>melitensis<\/jats:italic> 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 <jats:italic>Brucella<\/jats:italic>, and compared deletion mutants for these genes for their ability to protect mice against challenge with a virulent strain of <jats:italic>B<\/jats:italic>. <jats:italic>melitensis<\/jats:italic>. The protective efficacy of a deletion mutant for the <jats:italic>plsC<\/jats:italic> 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 <jats:italic>B<\/jats:italic>. <jats:italic>melitensis<\/jats:italic> faces different selective pressures depending on the organ and underscore the effectiveness of functional genome mapping for the design of new safer LAV candidates.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012459","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T20:51:30Z","timestamp":1724705490000},"page":"e1012459","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genome-wide analysis of Brucella melitensis growth in spleen of infected mice allows rational selection of new vaccine candidates"],"prefix":"10.1371","volume":"20","author":[{"given":"Emeline","family":"Barbieux","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Potemberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois-Xavier","family":"Stubbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Fraikin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katy","family":"Poncin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeline","family":"Reboul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Rouma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaia","family":"Z\u00fa\u00f1iga-Ripa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"De Bolle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1250-5228","authenticated-orcid":true,"given":"Eric","family":"Muraille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,26]]},"reference":[{"key":"ppat.1012459.ref001","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1600-065X.2010.00982.x","article-title":"An evolutionary strategy for a stealthy intracellular Brucella pathogen","author":"A Martirosyan","year":"2011","journal-title":"Immunological Reviews"},{"key":"ppat.1012459.ref002","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1146\/annurev-micro-090110-102905","article-title":"Interactions of the human pathogenic Brucella species with their hosts","volume":"65","author":"VL Atluri","year":"2011","journal-title":"Annu Rev 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