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To ensure safe clinical administration, deletion of certain genes, such as\n                      <jats:italic toggle=\"yes\">actA<\/jats:italic>\n                      , has been used to attenuate\n                      <jats:italic toggle=\"yes\">L. monocytogenes<\/jats:italic>\n                      -based vaccine strains while preserving immunogenicity. Here we explored the potential inclusion of a\n                      <jats:italic toggle=\"yes\">purA<\/jats:italic>\n                      gene deletion to enhance the development of\n                      <jats:italic toggle=\"yes\">L. monocytogenes<\/jats:italic>\n                      -based immunotherapy. The\n                      <jats:italic toggle=\"yes\">purA<\/jats:italic>\n                      gene encodes adenylosuccinate synthetase, which catalyzes the conversion of inosine monophosphate to adenosine monophosphate (AMP), a critical step in the\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      biosynthesis of purines. Since nucleotide biosynthesis is critical for the survival and pathogenesis of many bacterial pathogens, we examined the requirements of\n                      <jats:italic toggle=\"yes\">L. monocytogenes<\/jats:italic>\n                      AMP synthesis in tissue culture and animal infection models. The\n                      <jats:italic toggle=\"yes\">purA<\/jats:italic>\n                      mutants were able to escape from phagosomes of bone marrow-derived macrophages but were highly defective for subsequent growth in the host cell cytosol. In contrast to wild-type bacteria, the mutants did not grow in human serum or sheep blood. In intravenously infected mice,\n                      <jats:italic toggle=\"yes\">purA<\/jats:italic>\n                      mutants were highly attenuated, similar to\n                      <jats:italic toggle=\"yes\">actA<\/jats:italic>\n                      mutants, but displayed distinct growth kinetics during the course of infection. Remarkably, the\n                      <jats:italic toggle=\"yes\">purA<\/jats:italic>\n                      mutants exhibited different localization patterns across splenic immune cells and elicited a more potent CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell response compared to\n                      <jats:italic toggle=\"yes\">actA<\/jats:italic>\n                      mutants. These results underscore the essentiality of AMP biosynthesis for\n                      <jats:italic toggle=\"yes\">L. monocytogenes<\/jats:italic>\n                      pathogenesis and provide new avenues for developing safe\n                      <jats:italic toggle=\"yes\">L. monocytogenes<\/jats:italic>\n                      -based vaccines and therapeutics.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00343-25","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T14:18:33Z","timestamp":1757081913000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["<i>Listeria monocytogenes<\/i>\n                    adenosine auxotrophs are impaired for intracellular and extracellular growth but retain potent immunogenicity"],"prefix":"10.1128","volume":"93","author":[{"given":"Ying","family":"Feng","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cell Biology, University of California Berkeley","place":["Berkeley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3513-301X","authenticated-orcid":true,"given":"Mariya","family":"Lobanovska","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cell Biology, University of California Berkeley","place":["Berkeley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Vickery","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cell Biology, University of California Berkeley","place":["Berkeley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse Garcia","family":"Castillo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cell Biology, University of California Berkeley","place":["Berkeley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"G\u00fcereca","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cell Biology, University of California Berkeley","place":["Berkeley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon K.","family":"Chang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Plant and Microbial Biology, University of California Berkeley","place":["Berkeley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"DuPage","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cell Biology, University of California Berkeley","place":["Berkeley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1218-2799","authenticated-orcid":true,"given":"Daniel A.","family":"Portnoy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cell Biology, University of California Berkeley","place":["Berkeley, USA"]},{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Plant and Microbial Biology, University of California Berkeley","place":["Berkeley, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.126"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodcont.2016.12.016"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200205009"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","unstructured":"Ch\u00e1vez-Arroyo A Portnoy DA. 2020. 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