{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:22:41Z","timestamp":1785435761677,"version":"3.56.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"23","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01 AI063302"],"award-info":[{"award-number":["P01 AI063302"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI027655"],"award-info":[{"award-number":["R01 AI027655"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,9]]},"abstract":"<jats:p>\n                    Methylglyoxal is a reactive aldehyde produced by macrophages as part of their antimicrobial innate immune arsenal. Our prior work showed that\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">Listeria<\/jats:italic>\n                      monocytogenes\n                    <\/jats:italic>\n                    relies on glyoxalase A (GloA) and bacterial glutathione to detoxify methylglyoxal and that loss of GloA severely impairs bacterial virulence in mice and results in a 100 to 1,000 increase in bacterial mutation frequency. Glutathione is required for both methylglyoxal detoxification and for allosteric activation of the master virulence regulator PrfA, underscoring its central, yet complicated role in pathogenesis. We previously demonstrated that mutations that lock PrfA in its active conformation (PrfA*) rescue the virulence of\n                    <jats:italic toggle=\"yes\">gloA<\/jats:italic>\n                    mutants. Here, we show that PrfA* not only restores virulence but also rescues the elevated mutation frequency of\n                    <jats:italic toggle=\"yes\">gloA<\/jats:italic>\n                    mutants independently of canonical DNA repair pathways. We hypothesized that a PrfA-regulated gene mediates a GloA-independent mechanism to avoid the toxic effects of methylglyoxal and found that the absence of ActA abolished the PrfA*-mediated rescue of\n                    <jats:italic toggle=\"yes\">gloA<\/jats:italic>\n                    mutations. In addition, loss of ActA in a wild-type background also increased the in vivo mutation frequency of\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">L. monocytogenes<\/jats:italic>\n                      .\n                    <\/jats:italic>\n                    Since the primary role of ActA is to mediate bacterial cell-to-cell spread, we hypothesized that ActA allows\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">L. monocytogenes<\/jats:italic>\n                    <\/jats:italic>\n                    to migrate away from MG-rich inflammatory foci populated by activated macrophages. Indeed, antibody depletion of elicited macrophages and neutrophils rescued the virulence defect and reduced mutation frequency of\n                    <jats:italic toggle=\"yes\">gloA<\/jats:italic>\n                    mutants. We propose a model in which ActA-mediated actin-based motility allows\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">L. monocytogenes<\/jats:italic>\n                    <\/jats:italic>\n                    to spatially evade localized methylglyoxal production and hence outrun host defenses.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2534912123","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:10:26Z","timestamp":1780503026000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Host methylglyoxal activates the\n                    <i>Listeria<\/i>\n                    virulence program, allowing bacteria to evade inflammatory phagocytes by cell-to-cell spread"],"prefix":"10.1073","volume":"123","author":[{"given":"Andrea","family":"Anaya-Sanchez","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Microbiology Graduate Group, University of California","place":["Berkeley"]},{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Plant and Microbial Biology, University of California","place":["Berkeley"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preethi T.","family":"Ragunathan","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","place":["Berkeley"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Hung","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","place":["Berkeley"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Van Alst","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","place":["Berkeley"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3513-301X","authenticated-orcid":false,"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","place":["Berkeley"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4182-9048","authenticated-orcid":false,"given":"Sarah A.","family":"Stanley","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","place":["Berkeley"]},{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Disease and Vaccinology, School of Public Health, University of California","place":["Berkeley"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1218-2799","authenticated-orcid":false,"given":"Daniel A.","family":"Portnoy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Microbiology Graduate Group, University of California","place":["Berkeley"]},{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Plant and Microbial Biology, University of California","place":["Berkeley"]},{"id":[{"id":"https:\/\/ror.org\/01an7q238","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cell Biology, University of California","place":["Berkeley"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4274(99)00160-5"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.38.100184.000405"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00023"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3A0520-745RR"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2025.05.026"},{"key":"e_1_3_4_6_2","article-title":"Identification of glyoxalase A in group B","volume":"93","author":"Akbari M. 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