{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:08:51Z","timestamp":1788347331165,"version":"build-2803163510"},"reference-count":96,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The foodborne pathogen <jats:italic>Listeria monocytogenes<\/jats:italic> is able to survive across a wide range of intra- and extra-host environments by appropriately modulating gene expression patterns in response to different stimuli. Positive Regulatory Factor A (PrfA) is the major transcriptional regulator of virulence gene expression in <jats:italic>L<\/jats:italic>. <jats:italic>monocytogenes<\/jats:italic>. It has long been known that activated charcoal is required to induce the expression of PrfA-regulated genes in complex media, such as Brain Heart Infusion (BHI), but not in chemically defined media. In this study, we show that the expression of the PrfA-regulated <jats:italic>hly<\/jats:italic>, which encodes listeriolysin O, is induced 5- and 8-fold in <jats:italic>L<\/jats:italic>. <jats:italic>monocytogenes<\/jats:italic> cells grown in Chelex-treated BHI (Ch-BHI) and in the presence of activated charcoal (AC-BHI), respectively, relative to cells grown in BHI medium. Specifically, we show that metal ions present in BHI broth plays a role in the reduced expression of the PrfA regulon. In addition, we show that expression of <jats:italic>hly<\/jats:italic> is induced when the levels of bioavailable extra- or intercellular iron are reduced. <jats:italic>L<\/jats:italic>. <jats:italic>monocytogenes<\/jats:italic> cells grown Ch-BHI and AC-BHI media showed similar levels of resistance to the iron-activated antibiotic, streptonigrin, indicating that activated charcoal reduces the intracellular labile iron pool. Metal depletion and exogenously added glutathione contributed synergistically to PrfA-regulated gene expression since glutathione further increased <jats:italic>hly<\/jats:italic> expression in metal-depleted BHI but not in BHI medium. Analyses of transcriptional reporter fusion expression patterns revealed that genes in the PrfA regulon are differentially expressed in response to metal depletion, metal excess and exogenous glutathione. Our results suggest that metal ion abundance plays a role in modulating expression of PrfA-regulated virulence genes in <jats:italic>L<\/jats:italic>. <jats:italic>monocytogenes<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.pone.0250989","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T17:46:51Z","timestamp":1619718411000},"page":"e0250989","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Characterization of the roles of activated charcoal and Chelex in the induction of PrfA regulon expression in complex medium"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0246-4701","authenticated-orcid":true,"given":"Ahmed","family":"Gaballa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sriya","family":"Sunil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Doll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9092-0625","authenticated-orcid":true,"given":"Sarah I.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4149-3310","authenticated-orcid":true,"given":"Tyler","family":"Bechtel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Guariglia-Oropeza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4168-5662","authenticated-orcid":true,"given":"Martin","family":"Wiedmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"issue":"3","key":"pone.0250989.ref001","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1128\/MR.55.3.476-511.1991","article-title":"Listeria monocytogenes, a food-borne pathogen","volume":"55","author":"JM Farber","year":"1991","journal-title":"Microbiol Rev"},{"issue":"3","key":"pone.0250989.ref002","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1128\/CMR.14.3.584-640.2001","article-title":"Listeria pathogenesis and molecular virulence determinants","volume":"14","author":"JA Vazquez-Boland","year":"2001","journal-title":"Clin Microbiol Rev"},{"issue":"9","key":"pone.0250989.ref003","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nrmicro2171","article-title":"Listeria monocytogenes\u2014from saprophyte to intracellular pathogen","volume":"7","author":"NE Freitag","year":"2009","journal-title":"Nat Rev Microbiol"},{"issue":"5","key":"pone.0250989.ref004","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1128\/IAI.74.5.2505-2512.2006","article-title":"How the bacterial pathogen Listeria monocytogenes mediates the switch from environmental Dr. Jekyll to pathogenic Mr","volume":"74","author":"MJ Gray","year":"2006","journal-title":"Hyde. 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