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Manganese (Mn) acts as a cofactor for numerous enzymes and is crucial for bacterial oxidative stress resistance and virulence. However, excessive Mn is toxic, prompting bacteria to develop diverse Mn detoxification mechanisms. Herein, two genes (\n                      <jats:italic toggle=\"yes\">mneA<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">terC<\/jats:italic>\n                      ) located downstream of the Mn-sensing\n                      <jats:italic toggle=\"yes\">yybP-ykoY<\/jats:italic>\n                      riboswitch were identified in\n                      <jats:italic toggle=\"yes\">V. parahaemolyticus<\/jats:italic>\n                      . The expression of\n                      <jats:italic toggle=\"yes\">mneA<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">terC<\/jats:italic>\n                      is specifically induced by Mn. The\n                      <jats:italic toggle=\"yes\">mneA<\/jats:italic>\n                      deletion mutant (\u0394\n                      <jats:italic toggle=\"yes\">mneA<\/jats:italic>\n                      ) exhibited impaired growth in standard (pH 7.3), alkaline (pH 8.4), or weakly acidic (pH 6.8) medium supplemented with Mn. By contrast, the\n                      <jats:italic toggle=\"yes\">terC<\/jats:italic>\n                      deletion mutant (\u0394\n                      <jats:italic toggle=\"yes\">terC<\/jats:italic>\n                      ) showed growth inhibition under high Mn concentrations in weakly acidic medium. Furthermore, the\n                      <jats:italic toggle=\"yes\">mneA<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">terC<\/jats:italic>\n                      double mutant (\u0394\n                      <jats:italic toggle=\"yes\">mneA<\/jats:italic>\n                      \u0394\n                      <jats:italic toggle=\"yes\">terC<\/jats:italic>\n                      ) was more sensitive to Mn stress than \u0394\n                      <jats:italic toggle=\"yes\">mneA<\/jats:italic>\n                      . Bacterial survival assays revealed that both MneA and TerC protect\n                      <jats:italic toggle=\"yes\">V. parahaemolyticus<\/jats:italic>\n                      against Mn-induced bacteriostasis. Inductively coupled plasma-mass spectrometry showed that the deletion of\n                      <jats:italic toggle=\"yes\">mneA<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">terC<\/jats:italic>\n                      significantly increases intracellular Mn content. A competitive infection assay using a zebrafish model revealed that\n                      <jats:italic toggle=\"yes\">mneA<\/jats:italic>\n                      contributes to virulence in\n                      <jats:italic toggle=\"yes\">V. parahaemolyticus<\/jats:italic>\n                      , while\n                      <jats:italic toggle=\"yes\">terC<\/jats:italic>\n                      has no such effect. RNA sequencing analysis revealed that\n                      <jats:italic toggle=\"yes\">V. parahaemolyticus<\/jats:italic>\n                      modulates the expression of multiple genes in response to Mn bacteriostatic activity. Collectively, these findings indicate that MneA and TerC exhibit distinct roles in Mn detoxification and virulence in\n                      <jats:italic toggle=\"yes\">V. parahaemolyticus<\/jats:italic>\n                      . This work expands the understanding of Mn detoxification mechanisms in bacteria and highlights the role of Mn in the host\u2013pathogen interface.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Manganese (Mn) is important for life, but is toxic in excess. Consequently, bacteria have evolved elaborate mechanisms to maintain intracellular Mn homeostasis. In this study, we identified and characterized two Mn exporters, that is, MneA and TerC, in\n                        <jats:italic toggle=\"yes\">Vibrio parahaemolyticus<\/jats:italic>\n                        , a significant zoonotic pathogen. We showed that MneA and TerC protect\n                        <jats:italic toggle=\"yes\">V. parahaemolyticus<\/jats:italic>\n                        against Mn-induced bacteriostasis via Mn efflux. Strikingly, unlike the findings in\n                        <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                        that a TerC homolog Alx tunes intracellular Mn concentration at alkaline pH,\n                        <jats:italic toggle=\"yes\">V. parahaemolyticus<\/jats:italic>\n                        TerC facilitates the bacterium\u2019s growth under high Mn concentrations in weakly acidic medium. Moreover, MneA is crucial for the virulence of\n                        <jats:italic toggle=\"yes\">V. parahaemolyticus<\/jats:italic>\n                        , whereas TerC plays no apparent role. Collectively, while both MneA and TerC act as Mn exporters in\n                        <jats:italic toggle=\"yes\">V. parahaemolyticus<\/jats:italic>\n                        , they exhibit distinct roles. This study also highlights the importance of exploring conserved proteins in different bacterial species.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aem.01754-25","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T13:00:20Z","timestamp":1779282020000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["MneA and TerC exhibit distinct roles in manganese detoxification and virulence in\n                    <i>Vibrio parahaemolyticus<\/i>"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3030-4251","authenticated-orcid":true,"given":"Chengkun","family":"Zheng","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03tqb8s11","id-type":"ROR","asserted-by":"publisher"}],"name":"Jiangsu Key Laboratory of Zoonosis\/Jiangsu Co-Innovation Center for Prevention and 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