{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:35:23Z","timestamp":1792798523602,"version":"4.5.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32373063"],"award-info":[{"award-number":["32373063"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the science and technology program of Guangzhou, China","award":["202201010673"],"award-info":[{"award-number":["202201010673"]}]},{"name":"the innovative research groups of national natural science foundation of China","award":["32121004"],"award-info":[{"award-number":["32121004"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"MOST | National Key Research and Development Program of China","award":["2022YFD1800404"],"award-info":[{"award-number":["2022YFD1800404"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"published-print":{"date-parts":[[2024,11,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The dissemination of antibiotic resistance genes (ARGs) through plasmids is a major mechanism for the development of bacterial antimicrobial resistance. The adaptation and evolution mechanisms of multidrug-resistant (MDR) plasmids with their hosts are not fully understood. Herein, we conducted experimental evolution of a 244 kb MDR plasmid (pJXP9) under various conditions including no antibiotics and mono- or combinational drug treatments of colistin (CS), cefotaxime (CTX), and ciprofloxacin (CIP). Our results showed that long-term with or without positive selections for pJXP9, spanning approximately 600 generations, led to modifications of the plasmid-encoded MDR and conjugative transfer regions. These modifications could mitigate the fitness cost of plasmid carriage and enhance plasmid maintenance. The extent of plasmid modifications and the evolution of plasmid-encoded antibiotic resistance depended on treatment type, particularly the drug class and duration of exposure. Interestingly, prolonged exposure to mono- and combinational drugs of CS and CIP resulted in a substantial loss of the plasmid-encoded MDR region and antibiotic resistance, comparable to the selection condition without antibiotic. By contrast, combinational treatment with CTX contributed to the maintenance of the MDR region over a long period of time. Furthermore, drug selection was able to maintain and even amplify the corresponding plasmid-encoded ARGs, with co-selection of ARGs in the adjacent regions. In addition, parallel mutations in chromosomal\n                      <jats:italic>arcA<\/jats:italic>\n                      were also found to be associated with pJXP9 plasmid carriage among endpoint-evolved clones from diverse treatments. Meanwhile,\n                      <jats:italic>arcA<\/jats:italic>\n                      deletion improved the persistence of pJXP9 plasmid without drugs. Overall, our findings indicated that plasmid-borne MDR region deletion and chromosomal\n                      <jats:italic>arcA<\/jats:italic>\n                      inactivation mutation jointly contributed to co-adaptation and co-evolution between MDR IncHI2 plasmid and\n                      <jats:italic>Salmonella<\/jats:italic>\n                      Typhimurium under different drug selection pressure.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The plasmid-mediated dissemination of antibiotic resistance genes has become a significant concern for human health, even though the carriage of multidrug-resistant (MDR) plasmids is frequently associated with fitness costs for the bacterial host. However, the mechanisms by which MDR plasmids and bacterial pairs evolve plasmid-mediated antibiotic resistance in the presence of antibiotic selections are not fully understood. Herein, we conducted an experimental evolution of a large multidrug-resistant plasmid in a\n                        <jats:italic>Salmonella enterica<\/jats:italic>\n                        Typhimurium host under single and combinatorial drug selection pressures. Our results show the adaptive evolution of plasmid-encoded antibiotic resistance through alterations of the MDR region in the plasmid, in particular substantial loss of the MDR region, in response to different positive selections, especially mono- and combinational drugs of colistin and ciprofloxacin. In addition, strong parallel mutations in chromosomal\n                        <jats:italic>arcA<\/jats:italic>\n                        were associated with pJXP9 carriage in\n                        <jats:italic>Salmonella<\/jats:italic>\n                        Typhimurium from diverse treatments. Our results thus highlight promoting the loss of the plasmid\u2019s MDR region could offer an alternative approach for combating plasmid-encoded antibiotic resistance.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.01197-24","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T09:01:47Z","timestamp":1729587707000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Evolution and maintenance of a large multidrug-resistant plasmid in a\n                    <i>Salmonella enterica<\/i>\n                    Typhimurium host under differing antibiotic selection pressures"],"prefix":"10.1128","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5394-1156","authenticated-orcid":false,"given":"Ming","family":"Cheng","sequence":"first","affiliation":[{"name":"Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"name":"Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Jing","family":"Dai","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"name":"Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Fei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"name":"Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ting","family":"Su","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"name":"Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Qi","family":"Guo","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, College of Veterinary Medicine, South China Agricultural University","place":["Guangzhou, China"]},{"name":"Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5548-7147","authenticated-orcid":false,"given":"Ruan-Yang","family":"Sun","sequence":"additional","affiliation":[{"name":"Guangdong Laboratory for Lingnan Modern Agriculture, National Risk Assessment Laboratory for 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Investigation of factors influencing the successful persistence and dissemination of a globally distributed antibioticresistance plasmids. PhD thesis University of Birmingham Birmingham UK. https:\/\/etheses.bham.ac.uk\/id\/eprint\/3312\/"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.00110-21"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41559-022-01908-7"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03552-21"}],"container-title":["mSystems"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msystems.01197-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msystems.01197-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,25]],"date-time":"2024-12-25T07:36:37Z","timestamp":1735112197000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/msystems.01197-24"}},"subtitle":[],"editor":[{"given":"Christopher W.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,19]]},"references-count":42,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11,19]]}},"alternative-id":["10.1128\/msystems.01197-24"],"URL":"https:\/\/doi.org\/10.1128\/msystems.01197-24","relation":{},"ISSN":["2379-5077"],"issn-type":[{"value":"2379-5077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,19]]},"assertion":[{"value":"2024-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01197-24"}}