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They are inexpensive antibiotics, which have been used extensively in the prophlylaxis and therapy of human and animal infections and also at subtherapeutic levels in animal feed as growth promoters. The first tetracycline-resistant bacterium, Shigella dysenteriae, was isolated in 1953. Tetracycline resistance now occurs in an increasing number of pathogenic, opportunistic, and commensal bacteria. The presence of tetracycline-resistant pathogens limits the use of these agents in treatment of disease. Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Many of these genes are associated with mobile plasmids or transposons and can be distinguished from each other using molecular methods including DNA-DNA hybridization with oligonucleotide probes and DNA sequencing. A limited number of bacteria acquire resistance by mutations, which alter the permeability of the outer membrane porins and\/or lipopolysaccharides in the outer membrane, change the regulation of innate efflux systems, or alter the 16S rRNA. New tetracycline derivatives are being examined, although their role in treatment is not clear. Changing the use of tetracyclines in human and animal health as well as in food production is needed if we are to continue to use this class of broad-spectrum antimicrobials through the present century.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mmbr.65.2.232-260.2001","type":"journal-article","created":{"date-parts":[[2003,1,2]],"date-time":"2003-01-02T16:25:45Z","timestamp":1041524745000},"page":"232-260","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3809,"title":["Tetracycline Antibiotics: Mode of Action, Applications, Molecular Biology, and Epidemiology of Bacterial Resistance"],"prefix":"10.1128","volume":"65","author":[{"given":"Ian","family":"Chopra","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Antimicrobial Research Centre and Division of Microbiology, School of Biochemistry &amp; Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom,1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Roberts","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Department of Pathobiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington 98195-72382"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/24.Supplement_1.S17"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-8501-8_1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s100960050344"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1960.tb00170.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.10.2067"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1140"},{"key":"e_1_3_2_8_2","first-page":"1","article-title":"Report of the ASM task force on antibiotic resistance","volume":"1995","author":"American Society for Microbiology","year":"1995","unstructured":"American Society for Microbiology Report of the ASM task force on antibiotic resistance.Antimicrob. 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