{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:11:48Z","timestamp":1790665908270,"version":"4.1.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1046812"],"award-info":[{"award-number":["1046812"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1098337"],"award-info":[{"award-number":["1098337"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The soil-dwelling bacterium\n            <jats:named-content content-type=\"genus-species\">Burkholderia pseudomallei<\/jats:named-content>\n            is the causative agent of the potentially fatal disease melioidosis. The lack of a vaccine toward\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            means that melioidosis treatment relies on prolonged antibiotic therapy, which can last up to 6 months in duration or longer. Due to intrinsic resistance, few antibiotics are effective against\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            . The lengthy treatment regimen required increases the likelihood of resistance development, with subsequent potentially fatal relapse. Doxycycline (DOX) has historically played an important role in the eradication phase of melioidosis treatment. Both primary and acquired DOX resistances have been documented in\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            ; however, the molecular mechanisms underpinning DOX resistance have remained elusive. Here, we identify and functionally characterize the molecular mechanisms conferring acquired DOX resistance in an isogenic\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            pair. Two synergistic mechanisms were identified. The first mutation occurred in a putative\n            <jats:italic>S<\/jats:italic>\n            -adenosyl-\n            <jats:sc>l<\/jats:sc>\n            -methionine-dependent methyltransferase (encoded by\n            <jats:italic>BPSL3085<\/jats:italic>\n            ), which we propose leads to altered ribosomal methylation, thereby decreasing DOX binding efficiency. The second mutation altered the function of the efflux pump repressor gene,\n            <jats:italic>amrR<\/jats:italic>\n            , resulting in increased expression of the resistance-nodulation-division efflux pump, AmrAB-OprA. Our findings highlight the diverse mechanisms by which\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            can become resistant to antibiotics used in melioidosis therapy and the need for resistance monitoring during treatment regimens, especially in patients with prolonged or recrudesced positive cultures for\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.00268-17","type":"journal-article","created":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T00:40:52Z","timestamp":1490661652000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Loss of Methyltransferase Function and Increased Efflux Activity Leads to Doxycycline Resistance in Burkholderia pseudomallei"],"prefix":"10.1128","volume":"61","author":[{"given":"Jessica R.","family":"Webb","sequence":"first","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1079-4882","authenticated-orcid":false,"given":"Erin P.","family":"Price","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia"},{"name":"Centre for Animal Health Innovation, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Sippy Downs, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart J.","family":"Currie","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia"},{"name":"Department of Infectious Diseases and Northern Territory Medical Program, Royal Darwin Hospital, Darwin, Northern Territory, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6944-3980","authenticated-orcid":false,"given":"Derek S.","family":"Sarovich","sequence":"additional","affiliation":[{"name":"Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia"},{"name":"Centre for Animal Health Innovation, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Sippy Downs, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1204699"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00089-15"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu768"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2015.8"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-8579(00)00334-4"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.7.2082-2087.2003"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/24.3.295"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.12.116"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.8.1635"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/20.3.313"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S35529"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030789"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00139"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111020108"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.3.465"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000900"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.01.005"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1812.120638"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003586"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1086\/520218"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61951-0"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1407.071501"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.04.012"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2008.10.011"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01842-13"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2002.130687"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1086\/500137"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.65.2.232-260.2001"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14959-8"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00131-06"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1086\/650574"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00926-07"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01477-07"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt319"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000519"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084068"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.04.001"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.12.3940-3946.2002"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2008.12.011"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095918"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.000358"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03535-14"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.3402\/ljm.v6i0.5870"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018547"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.02456-14"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.2.565-570.2005"},{"key":"e_1_3_3_48_2","volume-title":"Methods for antimicrobial dilution and disk susceptibility testing of infrequently isolated or fastidious bacteria; approved guideline\u20143rd ed","author":"CLSI","year":"2015","unstructured":"CLSI. 2015. Methods for antimicrobial dilution and disk susceptibility testing of infrequently isolated or fastidious bacteria; approved guideline\u20143rd ed. Document M45-A2. CLSI, Wayne, PA."},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-7-618"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403302101"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200312000-00006"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.06737-11"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037723"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00268-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00268-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:40:19Z","timestamp":1645476019000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00268-17"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6]]},"references-count":56,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["10.1128\/AAC.00268-17"],"URL":"https:\/\/doi.org\/10.1128\/aac.00268-17","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6]]},"assertion":[{"value":"2017-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-03-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-05-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00268-17"}}