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A large plasmid of this type (pIP1202, ~80 Kb) has been isolated in a clinical isolate of\n              <jats:italic>Yersinia pestis<\/jats:italic>\n              , the agent of plague. Here, we report that pIP1202 was highly stable in\n              <jats:italic>Y. pestis-<\/jats:italic>\n              infected mice and fleas and did not reduce\n              <jats:italic>Y. pestis<\/jats:italic>\n              virulence in these animals. Although pIP1202 inflicted a fitness cost in fleas (but not in mice) when the insects fed on blood containing a mixture of plasmid-free and plasmid-bearing strains, such a co-infection scenario has never been reported in nature, indicating that pIP1202 could persist in\n              <jats:italic>Y. pestis<\/jats:italic>\n              strains. Despite being resistant to commonly used antibiotic treatments, we show that plague caused by\n              <jats:italic>Y. pestis<\/jats:italic>\n              harboring the pIP1202 plasmid is effectively cured by LPC-233\u2014a potent inhibitor of the essential LpxC enzyme in the lipid A biosynthetic pathway. Taken as a whole, our data highlight the alarming threat posed by\n              <jats:italic>Y. pestis<\/jats:italic>\n              harboring multidrug-resistant IncC plasmids that may persist in wild animals as a reservoir for long periods without antibiotic pressure and illuminate the impact of antibiotics with a novel mode of action against such a biothreat.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01497-24","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T14:00:21Z","timestamp":1738245621000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Assessing the threat of\n            <i>Yersinia pestis<\/i>\n            harboring a multi-resistant IncC plasmid and the efficacy of an antibiotic targeting LpxC"],"prefix":"10.1128","volume":"69","author":[{"given":"Nadine","family":"Lemaitre","sequence":"first","affiliation":[{"name":"Univ. of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019\u2014UMR 9017\u2014CIIL\u2014Center for Infection and Immunity of Lille","place":["Lille, France"]},{"name":"UR4294, Agents Infectieux, r\u00e9sistance et chimioth\u00e9rapie (AGIR), Universit\u00e9 de Picardie Jule Vernes","place":["Amiens, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Dewitte","sequence":"additional","affiliation":[{"name":"Univ. of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019\u2014UMR 9017\u2014CIIL\u2014Center for Infection and Immunity of Lille","place":["Lille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faniry","family":"Rakotomanimana","sequence":"additional","affiliation":[{"name":"Plague Unit, Institut Pasteur de Madagascar","place":["Antananarivo, Madagascar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gooden","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Duke University","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Toone","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Duke University","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoarisoa","family":"Rajerison","sequence":"additional","affiliation":[{"name":"Plague Unit, Institut Pasteur de Madagascar","place":["Antananarivo, Madagascar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7823-3416","authenticated-orcid":true,"given":"Pei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Duke University School of Medicine","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3811-9691","authenticated-orcid":true,"given":"Florent","family":"Sebbane","sequence":"additional","affiliation":[{"name":"Univ. of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019\u2014UMR 9017\u2014CIIL\u2014Center for Infection and Immunity of Lille","place":["Lille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199709043371004"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.06.031"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.129.3352.839"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2006.01492.x"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2319"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2018.06.007"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00525-20"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-89-2-383"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70059-7"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02573-14"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.580960"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plasmid.2018.09.010"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx488"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plasmid.2018.08.001"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05116-11"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000309"},{"key":"e_1_3_4_18_2","first-page":"423","article-title":"LXVII. 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