{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:43:53Z","timestamp":1779921833871,"version":"3.53.1"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2010,1,1]],"date-time":"2010-01-01T00:00:00Z","timestamp":1262304000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Tolerance is a poorly understood phenomenon that allows bacteria exposed to a bactericidal antibiotic to stop their growth and withstand drug-induced killing. This survival ability has been implicated in antibiotic treatment failures. Here, we describe a single nucleotide mutation (\n            <jats:italic>tol1<\/jats:italic>\n            ) in a tolerant\n            <jats:italic>Streptococcus gordonii<\/jats:italic>\n            strain (Tol1) that is sufficient to provide tolerance in vitro and in vivo. It induces a proline-to-arginine substitution (P483R) in the homodimerization interface of enzyme I of the sugar phosphotransferase system, resulting in diminished sugar uptake. In vitro, the susceptible wild-type (WT) and Tol1 cultures lost 4.5 and 0.6 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml, respectively, after 24 h of penicillin exposure. The introduction of\n            <jats:italic>tol1<\/jats:italic>\n            into the WT (WT P483R) conferred tolerance (a loss of 0.7 log\n            <jats:sub>10<\/jats:sub>\n            CFU\/ml\/24 h), whereas restitution of the parent sequence in Tol1 (Tol1 R483P) restored antibiotic susceptibility. Moreover, penicillin treatment of rats in an experimental model of endocarditis showed a complete inversion in the outcome, with a failure of therapy in rats infected with WT P483R and the complete disappearance of bacteria in animals infected with Tol1 R483P.\n          <\/jats:p>","DOI":"10.1128\/aac.00699-09","type":"journal-article","created":{"date-parts":[[2009,10,27]],"date-time":"2009-10-27T01:06:54Z","timestamp":1256605614000},"page":"259-266","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["A Single Mutation in Enzyme I of the Sugar Phosphotransferase System Confers Penicillin Tolerance to\n            <i>Streptococcus gordonii<\/i>"],"prefix":"10.1128","volume":"54","author":[{"given":"A.","family":"Bizzini","sequence":"first","affiliation":[{"name":"Department of Fundamental Microbiology, Faculty of Biology and Medicine, Biophore Building, University of Lausanne, Lausanne 1015, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"Entenza","sequence":"additional","affiliation":[{"name":"Department of Fundamental Microbiology, Faculty of Biology and Medicine, Biophore Building, University of Lausanne, Lausanne 1015, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Michielin","sequence":"additional","affiliation":[{"name":"Swiss Institute of Bioinformatics, Epalinges 1066, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, Bern 3012, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Erni","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, Bern 3012, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Moreillon","sequence":"additional","affiliation":[{"name":"Department of Fundamental Microbiology, Faculty of Biology and Medicine, Biophore Building, University of Lausanne, Lausanne 1015, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099390"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000221816"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.6.6.825"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi992679t"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm021"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002530000519"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi991250z"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540040211"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2002.tb11123.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.10.2802-2810.2000"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(88)90489-1"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.71.3.1364-1372.2005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02800.x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00015-06"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00024-06"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.12.007"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.8.2511-2514.2004"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/175.1.70"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)33508-7"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(86)90358-6"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2001.2603"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.25.5.575"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/7.3.368"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-0691.2003.00648.x"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1086\/318697"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.37.1.127-131.1982"},{"key":"e_1_3_2_28_2","first-page":"309","volume":"1","year":"1999","unstructured":"Hesterkamp, T., and B. 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