{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:00:44Z","timestamp":1790622044019,"version":"4.1.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2014,10,21]],"date-time":"2014-10-21T00:00:00Z","timestamp":1413849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,10,31]],"date-time":"2014-10-31T00:00:00Z","timestamp":1414713600000},"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":["mBio"],"published-print":{"date-parts":[[2014,10,31]]},"abstract":"ABSTRACT<\/jats:title>\n \n The amikacin resistance gene\n aphA6<\/jats:italic>\n was first detected in the nosocomial pathogen\n Acinetobacter baumannii<\/jats:named-content>\n and subsequently in other genera. Analysis of 133 whole-genome sequences covering the taxonomic diversity of\n Acinetobacter<\/jats:italic>\n spp. detected\n aphA6<\/jats:italic>\n in the chromosome of 2 isolates of\n A.\u00a0guillouiae<\/jats:italic>\n , which is an environmental species, 1 of 8\n A.\u00a0parvus<\/jats:italic>\n isolates, and 5 of 34\n A. baumannii<\/jats:named-content>\n isolates. The gene was also present in 29 out of 36\n A.\u00a0guillouiae<\/jats:italic>\n isolates screened by PCR, indicating that it is ancestral to this species. The\n P<\/jats:italic>\n native<\/jats:sub>\n promoter for\n aphA6<\/jats:italic>\n in\n A.\u00a0guillouiae<\/jats:italic>\n and\n A.\u00a0parvus<\/jats:italic>\n was replaced in\n A. baumannii<\/jats:named-content>\n by\n P<\/jats:italic>\n \n aphA6<\/jats:italic>\n <\/jats:sub>\n , which was generated by use of the insertion sequence IS\n Aba125<\/jats:italic>\n , which brought a \u221235 sequence. Study of promoter strength in\n Escherichia coli<\/jats:named-content>\n and\n A. baumannii<\/jats:named-content>\n indicated that\n P<\/jats:italic>\n \n aphA6<\/jats:italic>\n <\/jats:sub>\n was four times more potent than\n P<\/jats:italic>\n native<\/jats:sub>\n . There was a good correlation between aminoglycoside MICs and\n aphA6<\/jats:italic>\n transcription in\n A.\u00a0guillouiae<\/jats:italic>\n isolates that remained susceptible to amikacin. The marked topology differences of the phylogenetic trees of\n aphA6<\/jats:italic>\n and of the hosts strongly support its recent direct transfer within\n Acinetobacter<\/jats:italic>\n spp. and also to evolutionarily remote bacterial genera. Concomitant expression of\n aphA6<\/jats:italic>\n must have occurred because, contrary to the donors, it can confer resistance to the new hosts. Mobilization and expression of\n aphA6<\/jats:italic>\n via composite transposons and the upstream IS-generating hybrid\n P<\/jats:italic>\n \n aphA6<\/jats:italic>\n <\/jats:sub>\n , followed by conjugation, seems the most plausible mechanism. This is in agreement with the observation that, in the recipients,\n aphA6<\/jats:italic>\n is carried by conjugative plasmids and flanked by IS that are common in\n Acinetobacter<\/jats:italic>\n spp. Our data indicate that resistance genes can also be found in susceptible environmental bacteria.\n <\/jats:p>\n \n IMPORTANCE<\/jats:bold>\n We speculated that the\n aphA6<\/jats:italic>\n gene for an enzyme that confers resistance to amikacin, the most active aminoglycoside for the treatment of nosocomial infections due to\n Acinetobacter<\/jats:italic>\n spp., originated in this genus before disseminating to phylogenetically distant genera pathogenic for humans. Using a combination of whole-genome sequencing of a collection of\n Acinetobacter<\/jats:italic>\n spp. covering the breadth of the known taxonomic diversity of the genus, gene cloning, detailed promoter analysis, study of heterologous gene expression, and comparative analysis of the phylogenetic trees of\n aphA6<\/jats:italic>\n and of the bacterial hosts, we found that\n aphA6<\/jats:italic>\n originated in\n Acinetobacter guillouiae<\/jats:named-content>\n , an amikacin-susceptible environmental species. The gene conferred, upon mobilization, high-level resistance to the new hosts. This work stresses that nonpathogenic bacteria can act as reservoirs of resistance determinants, and it provides an example of the use of a genomic library to study the origin and dissemination of an antibiotic resistance gene to human pathogens.\n <\/jats:p>\n \u2009<\/jats:p>","DOI":"10.1128\/mbio.01972-14","type":"journal-article","created":{"date-parts":[[2014,10,22]],"date-time":"2014-10-22T06:14:11Z","timestamp":1413958451000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":51,"title":["Origin in Acinetobacter guillouiae and Dissemination of the Aminoglycoside-Modifying Enzyme Aph(3\u2032)-VI"],"prefix":"10.1128","volume":"5","author":[{"given":"Eun-Jeong","family":"Yoon","sequence":"first","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Agents Antibact\u00e9riens, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Goussard","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Agents Antibact\u00e9riens, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Touchon","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Microbial Evolutionary Genomics, Paris, France"},{"name":"CNRS, UMR 3525, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Krizova","sequence":"additional","affiliation":[{"name":"Laboratory of Bacterial Genetics, National Institute of Public Health, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Cerqueira","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Murphy","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Lambert","sequence":"additional","affiliation":[{"name":"EA4043, Facult\u00e9 de Pharmacie, Universit\u00e9 Paris Sud, Ch\u00e2tenay-Malabry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Grillot-Courvalin","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Agents Antibact\u00e9riens, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandr","family":"Nemec","sequence":"additional","affiliation":[{"name":"Laboratory of Bacterial Genetics, National Institute of Public Health, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Courvalin","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unit\u00e9 des Agents Antibact\u00e9riens, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1789"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02467-09"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0147-619X(83)90066-5"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.22.2.323"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020007"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00057-10"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.12.3375-3380.2001"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.8.2565-2571.2003"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.5.1577-1583.2003"},{"key":"e_1_3_4_11_2","first-page":"225","volume-title":"Antibiogram","author":"Lambert T","year":"2010","unstructured":"LambertT . 2010. 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