{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:46:47Z","timestamp":1791521207869,"version":"4.3.4"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":55,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP631632"],"award-info":[{"award-number":["APP631632"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1026922"],"award-info":[{"award-number":["APP1026922"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome Trust Seeding Drug Discovery","award":["094977\/Z\/10\/Z"],"award-info":[{"award-number":["094977\/Z\/10\/Z"]}]},{"DOI":"10.13039\/501100018833","name":"AID","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018833","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australia Awards Scholarship scholar"},{"name":"APEC-Australia Women in Research Fellowship 2022"},{"name":"AIMI Pathway Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and objectives<\/jats:title>\n                  <jats:p>The increasing occurrence of MRSA clinical isolates harbouring reduced susceptibility to mainstay antibiotics has escalated the use of second and last line antibiotics. Hence, it is critical to evaluate the likelihood of MRSA developing clinical resistance to these antibiotics. Our study sought to characterize the development of resistance to vancomycin (VAN), daptomycin (DAP) and linezolid (LZD) in MRSA ATCC 43300 in vitro and further determine the mechanisms underpinning resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>MRSA was exposed to increasing concentrations of VAN, DAP and LZD for 20\u2005days, with eight replicates for each antibiotic conducted in parallel. The resulting day 20 (D20) isolates were subjected to antimicrobial susceptibility testing, whole genome sequencing, autolysis assays, and growth curves to determine bacterial fitness.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Exposure to VAN or LZD for 20\u2005days resulted in a subtle 2-fold increase in the MIC, whereas DAP exposure yielded DAP-non-susceptible isolates with up to 16-fold MIC increase. The MIC increase was accompanied by variable changes in relative fitness and reduced resistance to autolysis in some isolates. D20 isolates harboured mutations in genes commonly associated with resistance to the respective antibiotics (e.g. walK for VAN, mprF and rpoB for DAP, rplC for LZD), along with several previously unreported variants. Introduction of key mutations to these identified genes in the parental strain via allelic exchange confirmed their role in the development of resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In vitro selection against VAN, DAP or LZD resulted in the acquisition of mutations similar to those correlated with clinical resistance, including the associated phenotypic alterations.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jacamr\/dlaf108","type":"journal-article","created":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T23:09:04Z","timestamp":1751152144000},"source":"Crossref","is-referenced-by-count":4,"title":["Characterisation of <i>in vitro<\/i> resistance selection against second-\/last-line antibiotics in methicillin-resistant <i>Staphylococcus aureus<\/i> ATCC 43300 strain"],"prefix":"10.1093","volume":"7","author":[{"given":"Anggia","family":"Prasetyoputri","sequence":"first","affiliation":[{"name":"Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland , Brisbane ,","place":["Australia"]},{"name":"Research Centre for Applied Microbiology, National Research and Innovation Agency , Cibinong ,","place":["Indonesia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda E","family":"Pitt","sequence":"additional","affiliation":[{"name":"Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland , Brisbane ,","place":["Australia"]},{"name":"Australian Institute for Microbiology and Infection, University of Technology Sydney , Ultimo, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4079-2383","authenticated-orcid":false,"given":"Minh Duc","family":"Cao","sequence":"additional","affiliation":[{"name":"Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumya","family":"Ramu","sequence":"additional","affiliation":[{"name":"Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Kavanagh","sequence":"additional","affiliation":[{"name":"Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alysha G","family":"Elliott","sequence":"additional","affiliation":[{"name":"Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devika","family":"Ganesamoorthy","sequence":"additional","affiliation":[{"name":"Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R","family":"Monk","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy P","family":"Stinear","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A","family":"Cooper","sequence":"additional","affiliation":[{"name":"Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland , Brisbane ,","place":["Australia"]},{"name":"Sitala Bio Ltd. , Unit D6, Grain House, Mill Ct., Shelford, Cambridgeshire CB22 1LD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4300-455X","authenticated-orcid":false,"given":"Lachlan J M","family":"Coin","sequence":"additional","affiliation":[{"name":"Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland , Brisbane ,","place":["Australia"]},{"name":"Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9447-2292","authenticated-orcid":false,"given":"Mark A 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