{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:49:35Z","timestamp":1791229775436,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"MRFF Artificial Heart Frontier Program"},{"DOI":"10.13039\/501100001779","name":"Monash University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001779","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Ventricular assist device driveline infections are difficult-to-treat diseases due to high antimicrobial resistance (AMR) of microbial biofilms. Multiple mechanisms of biofilm AMR have been proposed based on simplified in vitro models and demonstrated limited clinical implications. This study aimed to re-evaluate mechanisms contributing to staphylococcal biofilm AMR encountered in driveline infections and identify translatable therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A tunnel-based biofilm assay mimicking subcutaneous driveline infections was utilized to grow clinically relevant biofilms. Seven first-line antibiotics were investigated against biofilms formed by two staphylococcal laboratory reference strains. The importance of various biofilm AMR mechanisms was evaluated, including the barrier effect of the biofilm extracellular polymeric substance (EPS) matrix, high-cell-density growth, the presence of persister cells and repressed bacterial metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The presence of the EPS matrix couldn\u2019t decisively explain staphylococcal biofilm AMR in driveline infections. High-density growth and repressed bacterial metabolism appeared to be vital for biofilm AMR. Parallel comparisons of bacterial metabolic states and AMR at different biofilm developmental stages suggested a strong and negative correlation. Population profiling of tunnel-based biofilm cells identified subpopulations with low metabolic activity. Enhancing ATP production of biofilm cells partially restored their susceptibility to antibiotics. Local application of the weakly metabolism-dependent antibiotic gentamicin, but not the strongly metabolism-dependent vancomycin successfully killed staphylococcal biofilms in the simulated driveline tunnel, further underscoring the central role of bacterial metabolic repression in biofilm AMR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identified repressed bacterial metabolism as a central mechanism underpinning biofilm AMR and provided an effective therapeutic target for biofilm-associated driveline infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkaf316","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T11:49:46Z","timestamp":1755085786000},"page":"2923-2933","source":"Crossref","is-referenced-by-count":8,"title":["Low bacterial metabolism as a central mechanism of antimicrobial resistance and potential therapeutic target of staphylococcal biofilms in ventricular assist device driveline infections"],"prefix":"10.1093","volume":"80","author":[{"given":"Yao","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University; Wenzhou Medical University-Monash Biomedicine Discovery Institute Alliance in Clinical and Experimental Biomedicine , Wenzhou, Zhejiang Province 325000 ,","place":["China"]},{"name":"Infection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University , Clayton, Victoria 3800 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"McGiffin","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, The Alfred and Monash University , Melbourne, Victoria 3004 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Impact AMR, Monash University , Melbourne, Victoria 3800 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2171-4710","authenticated-orcid":false,"given":"Tieli","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University; Wenzhou Medical University-Monash Biomedicine Discovery Institute Alliance in Clinical and Experimental Biomedicine , Wenzhou, Zhejiang Province 325000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"To","family":"Nguyen Thi Nguyen","sequence":"additional","affiliation":[{"name":"Infection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University , Clayton, Victoria 3800 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Short","sequence":"additional","affiliation":[{"name":"Infection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University , Clayton, Victoria 3800 ,","place":["Australia"]},{"name":"Center to Impact AMR, Monash University , Melbourne, Victoria 3800 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton Y","family":"Peleg","sequence":"additional","affiliation":[{"name":"Infection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University , Clayton, Victoria 3800 ,","place":["Australia"]},{"name":"Department of Infectious Diseases, The Alfred Hospital and School of Translational Medicine, Monash University , Melbourne, Victoria 3004 ,","place":["Australia"]},{"name":"Center to Impact AMR, Monash University , Melbourne, Victoria 3800 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4683-708X","authenticated-orcid":false,"given":"Yue","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University; Wenzhou Medical University-Monash Biomedicine Discovery Institute Alliance in Clinical and Experimental Biomedicine , Wenzhou, Zhejiang Province 325000 ,","place":["China"]},{"name":"Infection Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University , Clayton, Victoria 3800 ,","place":["Australia"]},{"name":"Department of Infectious Diseases, The Alfred Hospital and School of Translational Medicine, Monash University , Melbourne, Victoria 3004 ,","place":["Australia"]},{"name":"Center to Impact AMR, Monash University , Melbourne, Victoria 3800 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