{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:10:37Z","timestamp":1781104237172,"version":"3.54.1"},"reference-count":23,"publisher":"National Academy of Sciences","issue":"42","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,10,16]]},"abstract":"<jats:p>\n                    EmrE, a multidrug antiporter from\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    , has presented biochemists with unusual surprises. Here we describe the transformation of EmrE, a drug\/H\n                    <jats:sup>+<\/jats:sup>\n                    antiporter to a polyamine importer by a single mutation. Antibiotic resistance in microorganisms may arise by mutations at certain chromosomal loci. To investigate this phenomenon, we used directed evolution of EmrE to assess the rate of development of novel specificities in existing multidrug transporters. Strikingly, when a library of random mutants of EmrE was screened for resistance to two major antibacterial drugs\u2014norfloxacin, a fluoroquinolone, and erythromycin, a macrolide\u2014 proteins with single mutations were found capable of conferring resistance. The mutation conferring erythromycin resistance resulted from substitution of a fully conserved and essential tryptophan residue to glycine, and, as expected, this protein lost its ability to recognize and transport the classical EmrE substrates. However, this protein functions now as an electrochemical potential driven importer of a new set of substrates: aliphatic polyamines. This mutant provides a unique paradigm to understand the function and evolution of distinct modes of transport.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1211831109","type":"journal-article","created":{"date-parts":[[2012,10,4]],"date-time":"2012-10-04T01:37:23Z","timestamp":1349314643000},"page":"16894-16899","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":41,"title":["Transforming a drug\/H\n                    <sup>+<\/sup>\n                    antiporter into a polyamine importer by a single mutation"],"prefix":"10.1073","volume":"109","author":[{"given":"Shlomo","family":"Brill","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, Alexander A. Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofir Sade","family":"Falk","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Alexander A. Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimon","family":"Schuldiner","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, Alexander A. Silberman Institute of Life Sciences, Hebrew University of Jerusalem, 91904 Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,10,3]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"crossref","unstructured":"C Nathan Fresh approaches to anti-infective therapies. Sci Transl Med 4:140sr2. 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