{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:10:56Z","timestamp":1791598256212,"version":"4.3.4"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T00:00:00Z","timestamp":1631664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["1.4.013.16.F"],"award-info":[{"award-number":["1.4.013.16.F"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["3.4.600.06.F"],"award-info":[{"award-number":["3.4.600.06.F"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fonds de la recherche scientifique - FNRS","award":["T.0060.15"],"award-info":[{"award-number":["T.0060.15"]}]},{"name":"FRS-FNRS"},{"name":"FRS-FNRS","award":["FRIA PhD grant"],"award-info":[{"award-number":["FRIA PhD grant"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Brucellosis is one of the most widespread bacterial zoonoses worldwide. Here, our aim was to identify the effector mechanisms controlling the early stages of intranasal infection with <jats:italic>Brucella<\/jats:italic> in C57BL\/6 mice. During the first 48 hours of infection, alveolar macrophages (AMs) are the main cells infected in the lungs. Using RNA sequencing, we identified the aconitate decarboxylase 1 gene (<jats:italic>Acod1<\/jats:italic>; also known as Immune responsive gene 1), as one of the genes most upregulated in murine AMs in response to <jats:italic>B<\/jats:italic>. <jats:italic>melitensis<\/jats:italic> infection at 24 hours post-infection. Upregulation of <jats:italic>Acod1<\/jats:italic> was confirmed by RT-qPCR in lungs infected with <jats:italic>B<\/jats:italic>. <jats:italic>melitensis<\/jats:italic> and <jats:italic>B<\/jats:italic>. <jats:italic>abortus<\/jats:italic>. We observed that <jats:italic>Acod1<\/jats:italic><jats:sup>-\/-<\/jats:sup> C57BL\/6 mice display a higher bacterial load in their lungs than wild-type (wt) mice following <jats:italic>B<\/jats:italic>. <jats:italic>melitensis<\/jats:italic> or <jats:italic>B<\/jats:italic>. <jats:italic>abortus<\/jats:italic> infection, demonstrating that <jats:italic>Acod1<\/jats:italic> participates in the control of pulmonary <jats:italic>Brucella<\/jats:italic> infection. The ACOD1 enzyme is mostly produced in mitochondria of macrophages, and converts cis-aconitate, a metabolite in the Krebs cycle, into itaconate. Dimethyl itaconate (DMI), a chemically-modified membrane permeable form of itaconate, has a dose-dependent inhibitory effect on <jats:italic>Brucella<\/jats:italic> growth <jats:italic>in vitro<\/jats:italic>. Interestingly, structural analysis suggests the binding of itaconate into the binding site of <jats:italic>B<\/jats:italic>. <jats:italic>abortus<\/jats:italic> isocitrate lyase. DMI does not inhibit multiplication of the isocitrate lyase deletion mutant \u0394<jats:italic>aceA B<\/jats:italic>. <jats:italic>abortus in vitro<\/jats:italic>. Finally, we observed that, unlike the wt strain, the \u0394<jats:italic>aceA B<\/jats:italic>. <jats:italic>abortus<\/jats:italic> strain multiplies similarly in wt and <jats:italic>Acod1<\/jats:italic><jats:sup>-\/-<\/jats:sup> C57BL\/6 mice. These data suggest that bacterial isocitrate lyase might be a target of itaconate in AMs.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009887","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T18:04:49Z","timestamp":1631729089000},"page":"e1009887","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Aconitate decarboxylase 1 participates in the control of pulmonary Brucella infection in mice"],"prefix":"10.1371","volume":"17","author":[{"given":"Aurore","family":"Demars","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5588-1664","authenticated-orcid":true,"given":"Armelle","family":"Vitali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7679-663X","authenticated-orcid":true,"given":"Audrey","family":"Comein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Carlier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulkader","family":"Azouz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7005-6195","authenticated-orcid":true,"given":"Stanislas","family":"Goriely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9261-8083","authenticated-orcid":true,"given":"Justine","family":"Smout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8906-3758","authenticated-orcid":true,"given":"V\u00e9ronique","family":"Flamand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9282-9857","authenticated-orcid":true,"given":"M\u00e9gane","family":"Van Gysel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4920-6857","authenticated-orcid":true,"given":"Johan","family":"Wouters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8229-3243","authenticated-orcid":true,"given":"Jan","family":"Abendroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0474-8003","authenticated-orcid":true,"given":"Thomas 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