{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T07:37:07Z","timestamp":1775547427927,"version":"3.50.1"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2008,11,1]],"date-time":"2008-11-01T00:00:00Z","timestamp":1225497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Most bacteria synthesize isoprenoids through one of two essential pathways which provide the basic building block, isopentyl diphosphate (IPP): either the classical mevalonate pathway or the alternative non-mevalonate 2-C-methyl-\n            <jats:sc>d<\/jats:sc>\n            -erythritol 4-phosphate (MEP) pathway. However, postgenomic analyses of the\n            <jats:italic>Listeria monocytogenes<\/jats:italic>\n            genome revealed that this pathogen possesses the genetic capacity to produce the complete set of enzymes involved in both pathways. The nonpathogenic species\n            <jats:italic>Listeria innocua<\/jats:italic>\n            naturally lacks the last two genes (\n            <jats:italic>gcpE<\/jats:italic>\n            and\n            <jats:italic>lytB<\/jats:italic>\n            ) of the MEP pathway, and bioinformatic analyses strongly suggest that the genes have been lost through evolution. In the present study we show that heterologous expression of\n            <jats:italic>gcpE<\/jats:italic>\n            and\n            <jats:italic>lytB<\/jats:italic>\n            in\n            <jats:italic>L. innocua<\/jats:italic>\n            can functionally restore the MEP pathway in this organism and confer on it the ability to induce V\u03b39V\u03b42 T cells. We have previously confirmed that both pathways are functional in\n            <jats:italic>L. monocytogenes<\/jats:italic>\n            and can provide sufficient IPP for normal growth in laboratory media (M. Begley, C. G. Gahan, A. K. Kollas, M. Hintz, C. Hill, H. Jomaa, and M. Eberl, FEBS Lett. 561:99-104, 2004). Here we describe a targeted mutagenesis strategy to create a double pathway mutant in\n            <jats:italic>L. monocytogenes<\/jats:italic>\n            which cannot grow in the absence of exogenously provided mevalonate, confirming the requirement for at least one intact pathway for growth. In addition, murine studies revealed that mutants lacking the MEP pathway were impaired in virulence relative to the parent strain during intraperitoneal infection, while mutants lacking the classical mevalonate pathway were not impaired in virulence potential. In vivo bioluminescence imaging also confirmed in vivo expression of the\n            <jats:italic>gcpE<\/jats:italic>\n            gene (MEP pathway) during murine infection.\n          <\/jats:p>","DOI":"10.1128\/iai.01376-07","type":"journal-article","created":{"date-parts":[[2008,9,3]],"date-time":"2008-09-03T01:11:35Z","timestamp":1220404295000},"page":"5392-5401","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["Analysis of the Isoprenoid Biosynthesis Pathways in\n            <i>Listeria monocytogenes<\/i>\n            Reveals a Role for the Alternative 2-C-Methyl-\n            <scp>d<\/scp>\n            -Erythritol 4-Phosphate Pathway in Murine Infection"],"prefix":"10.1128","volume":"76","author":[{"given":"Ma\u0301ire","family":"Begley","sequence":"first","affiliation":[{"name":"Alimentary Pharmabiotic Centre"},{"name":"Department of Microbiology, University College Cork"},{"name":"Teagasc Dairy Products Research Centre, Moorepark, Fermoy County Cork, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Bron","sequence":"additional","affiliation":[{"name":"Alimentary Pharmabiotic Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinead","family":"Heuston","sequence":"additional","affiliation":[{"name":"Alimentary Pharmabiotic Centre"},{"name":"Department of Microbiology, University College Cork"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pat G.","family":"Casey","sequence":"additional","affiliation":[{"name":"Alimentary Pharmabiotic Centre"},{"name":"Department of Microbiology, University College Cork"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Englert","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Klinische Chemie und Pathobiochemie, Justus-Liebig-Universita\u0308t Giessen, Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Wiesner","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Klinische Chemie und Pathobiochemie, Justus-Liebig-Universita\u0308t Giessen, Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan","family":"Jomaa","sequence":"additional","affiliation":[{"name":"Institut fu\u0308r Klinische Chemie und Pathobiochemie, Justus-Liebig-Universita\u0308t Giessen, Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cormac G. M.","family":"Gahan","sequence":"additional","affiliation":[{"name":"Alimentary Pharmabiotic Centre"},{"name":"Department of Microbiology, University College Cork"},{"name":"School of Pharmacy, University College Cork, Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Hill","sequence":"additional","affiliation":[{"name":"Alimentary Pharmabiotic Centre"},{"name":"Department of Microbiology, University College Cork"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02516-9"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2006.08.003"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(04)00131-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.02004.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.72.4.2876-2884.2006"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.2.1323-1338.2006"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(03)00074-1"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.2.1072-1083.2004"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2002.01414.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00483-6"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1134\/S0003683807020019"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.12.7736-7742.2001"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124234"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00758-06"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)03191-X"},{"key":"e_1_3_2_17_2","first-page":"528","volume":"8","year":"1990","unstructured":"Horton, R. 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