{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:20:11Z","timestamp":1784647211981,"version":"3.55.0"},"reference-count":0,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2000,12,1]],"date-time":"2000-12-01T00:00:00Z","timestamp":975628800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2000,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A novel class of tetracyclines, the glycylcyclines, have been shown to be active against bacterial strains harboring genes encoding tetracycline efflux pumps. However, two veterinary\n                    <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                    isolates that carried tetracycline resistance determinants of the\n                    <jats:italic toggle=\"yes\">tetA<\/jats:italic>\n                    (A) class were found to have reduced susceptibility to glycylcyclines, especially two early investigational glycylcyclines, DMG-MINO and DMG-DMDOT. These isolates were also quite resistant to tetracycline and minocycline. The isolates, one a strain of\n                    <jats:italic toggle=\"yes\">S. cholerasuis<\/jats:italic>\n                    and the other,\n                    <jats:italic toggle=\"yes\">S. typhimurium<\/jats:italic>\n                    , both carried the same novel\n                    <jats:italic toggle=\"yes\">tetA<\/jats:italic>\n                    (A) variant, based on DNA sequencing, with one determinant plasmid encoded and the other located on the chromosome. This\n                    <jats:italic toggle=\"yes\">tetA<\/jats:italic>\n                    (A) variant was cloned and shown to provide reduced susceptibility to the glycylcycline class although GAR-936, a glycylcycline currently in clinical development, was the least affected. The novel\n                    <jats:italic toggle=\"yes\">tetA<\/jats:italic>\n                    (A) gene carries two mutations in the largest cytoplasmic loop of the efflux pump, which causes a double frameshift in codons 201, 202, and 203. This \"interdomain region\" of the efflux pump has generally been regarded as having no functional role in the efflux of tetracycline but the double frameshift is most likely responsible for the enhanced resistance observed and points to an interaction that was previously unrecognized. Mutants of the\n                    <jats:italic toggle=\"yes\">tetA<\/jats:italic>\n                    (B) class with decreased susceptibility to the glycylcyclines were also generated\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . These all carried mutations in the portion of the\n                    <jats:italic toggle=\"yes\">tetA<\/jats:italic>\n                    (B) gene encoding a transmembrane spanning region of the efflux pump. The laboratory-generated mutants point to the tight constraints in substrate recognition of the transmembrane-spanning region and may suggest that it will be the interdomain region of the pump that is likely to be the locus of future glycylcycline resistance mutations as these compounds enter clinical use.\n                  <\/jats:p>","DOI":"10.1089\/mdr.2000.6.277","type":"journal-article","created":{"date-parts":[[2009,1,28]],"date-time":"2009-01-28T15:35:48Z","timestamp":1233156948000},"page":"277-282","source":"Crossref","is-referenced-by-count":73,"title":["Mutations in the Interdomain Loop Region of the\n                    <i>tetA<\/i>\n                    (A) Tetracycline Resistance Gene Increase Efflux of Minocycline and Glycylcyclines"],"prefix":"10.1177","volume":"6","author":[{"given":"Margareta","family":"Tuckman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Projan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2000,12]]},"container-title":["Microbial Drug Resistance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/mdr.2000.6.277","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/mdr.2000.6.277","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:13:49Z","timestamp":1770747229000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.1089\/mdr.2000.6.277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,12]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2000,12]]}},"alternative-id":["10.1089\/mdr.2000.6.277"],"URL":"https:\/\/doi.org\/10.1089\/mdr.2000.6.277","relation":{},"ISSN":["1076-6294","1931-8448"],"issn-type":[{"value":"1076-6294","type":"print"},{"value":"1931-8448","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,12]]}}}