{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T16:31:37Z","timestamp":1786379497125,"version":"build-2736575974"},"reference-count":45,"publisher":"Microbiology Society","issue":"8","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"crossref","award":["R01 DE032555"],"award-info":[{"award-number":["R01 DE032555"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"crossref","award":["T90 DE021990"],"award-info":[{"award-number":["T90 DE021990"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"crossref","award":["F31 DE032899"],"award-info":[{"award-number":["F31 DE032899"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:p>\n                    Recently, our group showed that the dental pathogen\n                    <jats:italic>Streptococcus mutans<\/jats:italic>\n                    is inherently more tolerant to high zinc stress than other streptococci, a phenotype associated with the presence of a P-type ATPase exporter named ZccE, virtually unique to\n                    <jats:italic>S. mutans<\/jats:italic>\n                    . In addition to\n                    <jats:italic>zccE<\/jats:italic>\n                    , a previous transcriptome analysis revealed that\n                    <jats:italic>S. mutans<\/jats:italic>\n                    upregulates genes involved in glutathione uptake during initial exposure to zinc stress. Glutathione, a major supplier of organic sulphur that also plays key roles in antioxidant defence and xenobiotic detoxification, forms coordination complexes with a variety of metals, including zinc, thereby functioning as a buffer that protects cells from metal intoxication. To investigate the contribution of glutathione zinc tolerance in\n                    <jats:italic>S. mutans<\/jats:italic>\n                    , the\n                    <jats:italic>gshT<\/jats:italic>\n                    gene, which encodes the substrate-binding subunit of a glutathione transporter, was deleted in both the parent and \u0394\n                    <jats:italic>zccE<\/jats:italic>\n                    strains, and the ability of these mutants to overcome zinc stress through intracellular glutathione accumulation was determined. Targeted metabolomics revealed that\n                    <jats:italic>S. mutans<\/jats:italic>\n                    accumulates glutathione in a GshT-dependent manner following zinc stress, a response that was strikingly amplified in the \u0394\n                    <jats:italic>zccE<\/jats:italic>\n                    strain. Although glutathione supplementation had a minimal impact on the growth of either parent or mutant strains in sub-inhibitory zinc concentrations, the \u0394\n                    <jats:italic>gshT<\/jats:italic>\n                    strain exhibited increased zinc sensitivity in a plate-based assay. However, the \u0394\n                    <jats:italic>zccE<\/jats:italic>\n                    \u0394\n                    <jats:italic>gshT<\/jats:italic>\n                    mutant displayed enhanced zinc tolerance compared to the \u0394\n                    <jats:italic>zccE<\/jats:italic>\n                    single mutant. While glutathione alone did not alter zinc levels in the UA159 or \u0394\n                    <jats:italic>zccE<\/jats:italic>\n                    strains, the combination of zinc and glutathione nearly doubled intracellular zinc levels in \u0394\n                    <jats:italic>zccE<\/jats:italic>\n                    compared to cells grown in zinc only. We conclude that while glutathione may play a minor role in\n                    <jats:italic>S. mutans<\/jats:italic>\n                    zinc tolerance, enhanced glutathione uptake observed in \u0394\n                    <jats:italic>zccE<\/jats:italic>\n                    facilitates zinc entry, as glutathione:Zn\n                    <jats:sup>2+<\/jats:sup>\n                    complexes inadvertently promote zinc intoxication via a Trojan horse mechanism.\n                  <\/jats:p>","DOI":"10.1099\/mic.0.001754","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T16:16:17Z","timestamp":1786378577000},"source":"Crossref","is-referenced-by-count":0,"title":["Zinc tolerance through glutathione import strikes a fine balance between protection and damage in Streptococcus mutans"],"prefix":"10.1099","volume":"172","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6711-0779","authenticated-orcid":false,"given":"Miranda C.","family":"Carter","sequence":"first","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2187-4367","authenticated-orcid":false,"given":"Edroyal","family":"Womack","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0681-1927","authenticated-orcid":false,"given":"Malak","family":"Khatib","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1124-3385","authenticated-orcid":false,"given":"Alexandra M.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4642-8956","authenticated-orcid":false,"given":"Irene S.","family":"Saengpet","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-5863","authenticated-orcid":false,"given":"Jose A.","family":"Lemos","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.02.12.24302677"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.GPP3-0051-2018"},{"key":"R3","first-page":"141","article-title":"On the bacterial factor in the \u00e6tiology of dental caries","volume":"5","author":"Clarke","year":"1924","journal-title":"Br J Exp Pathol"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms12010121"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00257-22"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2836"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2019.06.010"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.15"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00745-6"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2016.03.022"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1039\/jr9530003192"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006515"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-0921"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.3390\/nu10010016"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.3390\/nu18040557"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.3390\/medicina59122088"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2005.01.003"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051x.1975.tb01724.x"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010477"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00276-08"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02804-20"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01393-12"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2008.08.006"},{"key":"R24","doi-asserted-by":"crossref","first-page":"567","DOI":"10.18388\/abp.1999_4129","article-title":"Coordination chemistry of glutathione","volume":"46","author":"Krezel","year":"1999","journal-title":"Acta Biochim Pol"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.753"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.7.2131-2135.1996"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00271-08"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12274"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1016\/s0167-7012(01)00369-4"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1016\/j.mimet.2015.09.023"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1318"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00535-20"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00764-19"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12337"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089427"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002357"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12405"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.22.6876-6881.1999"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1093\/mtomcs\/mfab015"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.6.1454-1459.1998"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1177\/0022034513498598"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00367-19"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.7.1990-1995.1996"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00272-08"}],"container-title":["Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/micro\/10.1099\/mic.0.001754?crawler=true&mimetype=application\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T16:16:20Z","timestamp":1786378580000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/micro\/10.1099\/mic.0.001754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":45,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,10]]}},"URL":"https:\/\/doi.org\/10.1099\/mic.0.001754","relation":{},"ISSN":["1350-0872","1465-2080"],"issn-type":[{"value":"1350-0872","type":"print"},{"value":"1465-2080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]}}}