{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:39:43Z","timestamp":1791297583956,"version":"4.1.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"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":[[2015,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Amdinocillin (mecillinam) is a \u03b2-lactam antibiotic that is used mainly for the treatment of uncomplicated urinary tract infections. The objectives of this study were to identify mutations that confer amdinocillin resistance on laboratory-isolated mutants and clinical isolates of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n                    and to determine why amdinocillin resistance remains rare clinically even though resistance is easily selected in the laboratory. Under laboratory selection, frequencies of mutation to amdinocillin resistance varied from 8 \u00d7 10\n                    <jats:sup>\u22128<\/jats:sup>\n                    to 2 \u00d7 10\n                    <jats:sup>\u22125<\/jats:sup>\n                    per cell, depending on the concentration of amdinocillin used during selection. Several genes have been demonstrated to give amdinocillin resistance, but here eight novel genes previously unknown to be involved in amdinocillin resistance were identified. These genes encode functions involved in the respiratory chain, the ribosome, cysteine biosynthesis, tRNA synthesis, and pyrophosphate metabolism. The clinical isolates exhibited significantly greater fitness than the laboratory-isolated mutants and a different mutation spectrum. The\n                    <jats:italic>cysB<\/jats:italic>\n                    gene was mutated (inactivated) in all of the clinical isolates, in contrast to the laboratory-isolated mutants, where mainly other types of more costly mutations were found. Our results suggest that the frequency of mutation to amdinocillin resistance is high because of the large mutational target (at least 38 genes). However, the majority of these resistant mutants have a low growth rate, reducing the probability that they are stably maintained in the bladder. Inactivation of the\n                    <jats:italic>cysB<\/jats:italic>\n                    gene and a resulting loss of cysteine biosynthesis are the major mechanism of amdinocillin resistance in clinical isolates of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. coli<\/jats:named-content>\n                    .\n                  <\/jats:p>","DOI":"10.1128\/aac.04819-14","type":"journal-article","created":{"date-parts":[[2015,2,11]],"date-time":"2015-02-11T13:35:13Z","timestamp":1423661713000},"page":"1718-1727","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":100,"title":["Amdinocillin (Mecillinam) Resistance Mutations in Clinical Isolates and Laboratory-Selected Mutants of Escherichia coli"],"prefix":"10.1128","volume":"59","author":[{"given":"Elisabeth","family":"Thulin","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Sundqvist","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Clinical Microbiology, \u00d6rebro University Hospital, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan I.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"UVI_rek1-8","author":"Anonymous","year":"2005","unstructured":"Anonymous. 2005. UVI_rek1-8. L\u00e4kemedelsverket Medical Products Agency, Uppsala, Sweden. http:\/\/www.lakemedelsverket.se\/malgrupp\/Halso---sjukvard\/Behandlings--rekommendationer\/Behandlingsrekommendation---listan\/UVI---Nedre-urinvagsinfektion-hos-kvinnor\/."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq257"},{"key":"e_1_3_3_4_2","first-page":"135","article-title":"6\u03b2-Amidinopenicillanic acids\u2014a new group of antibiotics","volume":"236","author":"Lund F","year":"1972","unstructured":"Lund F, Tybring L. 1972. 6\u03b2-Amidinopenicillanic acids\u2014a new group of antibiotics. Nature 236:135\u2013137.","journal-title":"Nature"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.8.3.271"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/46.suppl_1.35"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.6026.14"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.18.6.952"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2004.00737.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(01)00066-4"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.141.1.52-57.1980"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/3.suppl_B.13"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2677"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2007.06.007"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.8.2999"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg028"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2011.09.013"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2008.05.010"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.169.11.4935-4940.1987"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.133.1.196-202.1978"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.171.1.558-560.1989"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.20.6704-6710.1993"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/156.4.1483"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05194.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00279366"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.24.7650a-7650a.1999"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.137.2.839-845.1979"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.170.1.65-70.1988"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1995.tb02421.x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2001.tb10716.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01740-07"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.15.4524-4527.1995"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2006.00133.x"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1994.tb00482.x"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.13.3818-3828.1996"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.4.966-972.1994"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00974.x"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02818972"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2005.03.008"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04122.x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02986080"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.120163297"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2006.04.018"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07657.x"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(95)00193-A"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1186\/1754-1611-3-4"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(87)90127-2"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/1754-1611-2-5"},{"key":"e_1_3_3_49_2","volume-title":"R: a language and environment for statistical computing","author":"R Development Core Team","year":"2012","unstructured":"R Development Core Team. 2012. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria."},{"key":"e_1_3_3_50_2","volume-title":"SWEDRES 2010. A report on Swedish antimicrobial utilisation and resistance in human medicine","author":"Hellman J","year":"2010","unstructured":"Hellman J, Norman C, Olsson-Liljequist B. 2010. SWEDRES 2010. A report on Swedish antimicrobial utilisation and resistance in human medicine. Swedish Institute for Communicable Disease Control, Solna, Sweden. http:\/\/www.strama.se\/uploads\/docs\/Swedres%202010%20final.pdf."},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.172.10.5686-5689.1990"},{"key":"e_1_3_3_52_2","volume-title":"Brock biology of microorganisms","author":"Madigan MT","year":"2007","unstructured":"Madigan MT, Martinko JM, Dunlap PV, Clark DP. 2007. Brock biology of microorganisms, 12th ed. Benjamin Cummings, San Francisco, CA.","edition":"12"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.47.2.169-178.1983"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00427-6"},{"key":"e_1_3_3_55_2","first-page":"514","volume-title":"Escherichia coli and Salmonella: cellular and molecular biology","author":"Kredich NM","year":"1996","unstructured":"Kredich NM. 1996. Biosynthesis of cysteine, p 514\u2013527. In Neidhardt FC, Curtiss R, III, Ingraham JL, Lin ECC, Low KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE (ed), Escherichia coli and Salmonella: cellular and molecular biology, 2nd ed, vol 1. ASM Press, Washington, DC.","edition":"2"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1992.tb01500.x"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.04819-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.04819-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T17:52:16Z","timestamp":1645465936000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.04819-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3]]},"references-count":55,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1128\/AAC.04819-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.04819-14","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.725312214.793505146","asserted-by":"object"}]},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3]]},"assertion":[{"value":"2014-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-01-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}