{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:11:31Z","timestamp":1791277891397,"version":"4.1.0"},"reference-count":18,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2005,8,1]],"date-time":"2005-08-01T00:00:00Z","timestamp":1122854400000},"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":[[2005,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Capreomycin, kanamycin, amikacin, and viomycin are drugs that are used to treat multidrug-resistant tuberculosis. Each inhibits translation, and cross-resistance to them is a concern during therapy. A recent study revealed that mutation of the\n            <jats:italic>tlyA<\/jats:italic>\n            gene, encoding a putative rRNA methyltransferase, confers capreomycin and viomycin resistance in\n            <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n            bacteria. Mutations in the 16S rRNA gene (\n            <jats:italic>rrs<\/jats:italic>\n            ) have been associated with resistance to each of the drugs; however, reports of cross-resistance to the drugs have been variable. We investigated the role of\n            <jats:italic>rrs<\/jats:italic>\n            mutations in capreomycin resistance and examined the molecular basis of cross-resistance to the four drugs in\n            <jats:italic>M. tuberculosis<\/jats:italic>\n            laboratory-generated mutants and clinical isolates. Spontaneous mutants were generated to the drugs singularly and in combination by plating on medium containing one or two drugs. The frequencies of recovery of the mutants on single- and dual-drug plates were consistent with single-step mutations. The\n            <jats:italic>rrs<\/jats:italic>\n            genes of all mutants were sequenced, and the\n            <jats:italic>tlyA<\/jats:italic>\n            genes were sequenced for mutants selected on capreomycin, viomycin, or both; MICs of all four drugs were determined. Three\n            <jats:italic>rrs<\/jats:italic>\n            mutations (A1401G, C1402T, and G1484T) were found, and each was associated with a particular cross-resistance pattern. Similar mutations and cross-resistance patterns were found in drug-resistant clinical isolates. Overall, the data implicate\n            <jats:italic>rrs<\/jats:italic>\n            mutations as a molecular basis for resistance to each of the four drugs. Furthermore, the genotypic and phenotypic differences seen in the development of cross-resistance when\n            <jats:italic>M. tuberculosis<\/jats:italic>\n            bacteria were exposed to one or two drugs have implications for selection of treatment regimens.\n          <\/jats:p>","DOI":"10.1128\/aac.49.8.3192-3197.2005","type":"journal-article","created":{"date-parts":[[2005,7,27]],"date-time":"2005-07-27T10:52:45Z","timestamp":1122461565000},"page":"3192-3197","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":237,"title":["Molecular Analysis of Cross-Resistance to Capreomycin, Kanamycin, Amikacin, and Viomycin in\n            <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1128","volume":"49","author":[{"given":"Courtney E.","family":"Maus","sequence":"first","affiliation":[{"name":"Program in Microbiology and Molecular Genetics, Emory University, Atlanta, Georgia 30322"},{"name":"Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie B.","family":"Plikaytis","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Shinnick","sequence":"additional","affiliation":[{"name":"Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.5.1295"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0041-3879(83)90035-1","volume":"64","year":"1983","unstructured":"Allen, B. W., D. A. Mitchison, Y. C. Chan, W. W. Yew, W. G. Allan, and D. J. Girling. 1983. Amikacin in the treatment of pulmonary tuberculosis. Tubercle64:111-118.","journal-title":"Tubercle"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-10-2967"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1989.tb03494.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.7883\/yoken1952.16.31","volume":"16","year":"1963","unstructured":"Koseki, Y., and S. Okamoto. 1963. Studies on cross-resistance between capreomycin and certain other anti-mycobacterial agents. Jpn. J. Med. Sci. Biol.16:31-38.","journal-title":"Jpn. J. Med. Sci. Biol."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.9.2971-2973.2003"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.2.571-577.2005"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0041-3879(77)80007-X","volume":"58","year":"1977","unstructured":"McClatchy, J. K., W. Kanes, P. T. Davidson, and T. S. Moulding. 1977. Cross-resistance in M. tuberculosis to kanamycin, capreomycin and viomycin. Tubercle58:29-34.","journal-title":"Tubercle"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1111\/j.1749-6632.1966.tb45539.x","volume":"135","year":"1966","unstructured":"Morse, W. C., E. F. Sproat, C. W. Arrington, and J. A. Hawkins. 1966. M. tuberculosis in vitro susceptibility and serum level experiences with capreomycin. Ann. N. Y. Acad. Sci.135:983-988.","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"e_1_3_2_11_2","unstructured":"NCCLS. 2003 Susceptibility testing of mycobacteria nocardiae and other aerobic actinomycetes; approved standard M24-A. NCCLS Wayne Pa."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.5.1037-1043.1998"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/515328"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1966.tb45536.x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.36.5.1220-1225.1998"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.15.4795-4801.1997"},{"key":"e_1_3_2_17_2","first-page":"780","volume":"99","year":"1969","unstructured":"Tsukamura, M. 1969. Cross-resistance relationships between capreomycin, kanamycin, and viomycin resistances in tubercle bacilli from patients. Am. Rev. Respir. Dis.99:780-782.","journal-title":"Am. Rev. Respir. Dis."},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1099\/00221287-88-2-269","volume":"88","year":"1975","unstructured":"Tsukamura, M., and S. Mizuno. 1975. Cross-resistant relationships among the aminoglucoside antibiotics in Mycobacterium tuberculosis. J. Gen. Microbiol.88:269-274.","journal-title":"J. Gen. Microbiol."},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.7164\/antibiotics.29.1124","volume":"29","year":"1976","unstructured":"Yamada, T., Y. Mizuguchi, and K. Suga. 1976. Localization of co-resistance to streptomycin, kanamycin, capreomycin, and tuberactinomycin in core particles derived from ribosomes of viomycin-resistant Mycobacterium smegmatis. J. Antibiot. (Tokyo)29:1124-1126.","journal-title":"J. Antibiot. 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