{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:44:30Z","timestamp":1790232270664,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,7,13]],"date-time":"2014-07-13T00:00:00Z","timestamp":1405209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM099667"],"award-info":[{"award-number":["GM099667"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2014,8]]},"abstract":"Summary<\/jats:title>A B<\/jats:italic><\/jats:styled-content>radyrhizobium japonicum<\/jats:italic> mutant defective in the gene encoding the high\u2010affinity Mn<\/jats:styled-content>2+<\/jats:sup> transporter MntH<\/jats:styled-content> has a severe growth phenotype under manganese limitation. Here, we isolated suppressor mutants of an mntH<\/jats:italic><\/jats:styled-content> strain that grew under manganese limitation, and activities of high\u2010affinity Mn<\/jats:styled-content>2+<\/jats:sup> transport and Mn<\/jats:styled-content>2+<\/jats:sup>\u2010dependent enzymes were partially rescued. The suppressor strains harbour gain\u2010of\u2010function mutations in the gene encoding the Mg<\/jats:styled-content>2+<\/jats:sup> channel MgtE<\/jats:styled-content>. The MgtE<\/jats:styled-content> variants likely allow Mn<\/jats:styled-content>2+<\/jats:sup> entry via loss of a gating mechanism that normally holds the transporter in the closed state when cellular Mg<\/jats:styled-content>2+<\/jats:sup> levels are high. Both MgtE<\/jats:styled-content>\u2010dependent and MgtE<\/jats:styled-content>\u2010independent suppressor phenotypes were recapitulated by magnesium\u2010limited growth of the mntH<\/jats:italic><\/jats:styled-content> strain. Growth studies of wild\u2010type cells suggest that manganese is toxic to cells when environmental magnesium is low. Moreover, extracellular manganese and magnesium levels were manipulated to inhibit growth without substantially altering the intracellular content of either metal, implying that manganese toxicity depends on its cellular distribution rather than the absolute concentration. Mg<\/jats:styled-content>2+<\/jats:sup>\u2010dependent enzyme activities were found to be inhibited or stimulated by Mn<\/jats:styled-content>2+<\/jats:sup>. We conclude that Mn<\/jats:styled-content>2+<\/jats:sup> can occupy Mg<\/jats:styled-content>2+<\/jats:sup> binding sites in cells, and suggest that Mg<\/jats:styled-content>2+<\/jats:sup>\u2010dependent processes are targets of manganese toxicity.<\/jats:p>","DOI":"10.1111\/mmi.12687","type":"journal-article","created":{"date-parts":[[2014,6,26]],"date-time":"2014-06-26T15:53:17Z","timestamp":1403797997000},"page":"736-747","source":"Crossref","is-referenced-by-count":50,"title":["Magnesium\u2010dependent processes are targets of bacterial manganese toxicity"],"prefix":"10.1111","volume":"93","author":[{"given":"Thomas H.","family":"Hohle","sequence":"first","affiliation":[{"name":"Department of Biochemistry State University of New York at Buffalo Buffalo NY 14214 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"O'Brian","sequence":"additional","affiliation":[{"name":"Department of Biochemistry State University of New York at Buffalo Buffalo NY 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