{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:09:12Z","timestamp":1787612952470,"version":"build-2736575974"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100005795","name":"Chang Gung Memorial Hospital, Linkou","doi-asserted-by":"publisher","award":["CMRPD1J0271-3"],"award-info":[{"award-number":["CMRPD1J0271-3"]}],"id":[{"id":"10.13039\/501100005795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["110-2320-B-182-019-MY3"],"award-info":[{"award-number":["110-2320-B-182-019-MY3"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,10,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Lugdunin, produced by\n                      <jats:italic toggle=\"yes\">Staphylococcus lugdunensis<\/jats:italic>\n                      , exhibits potent antimicrobial activity against a broad range of Gram-positive bacteria, including\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      . This study aims to elucidate the mechanisms underlying the susceptibility of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      to lugdunin by screening a transposon-based mutant library generated using the lugdunin-susceptible\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      strain HG001. We identified four\n                      <jats:italic toggle=\"yes\">S<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">aureus<\/jats:italic>\n                      mutants with mutations in\n                      <jats:italic toggle=\"yes\">ctaA<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">hemY<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">qoxA<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">guaB<\/jats:italic>\n                      , which are involved in ATP and GTP synthesis, and displayed increased susceptibility to\n                      <jats:italic toggle=\"yes\">S. lugdunensis<\/jats:italic>\n                      . Further tests using synthetic lugdunin confirmed that energy generation defects make\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      more susceptible to lugdunin. Moreover, these mutants displayed small colony variant (SCV) phenotypes, a slow-growing form of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      characterized by altered metabolism, revealing the critical role of energy metabolism in\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      defense mechanisms. Furthermore, we observed that clinical SCV isolates exhibited greater susceptibility to lugdunin compared to their parental strains. Additionally, lugdunin treatment enhanced SCV susceptibility to commonly used antibiotics, including oxacillin and vancomycin, suggesting a synergistic effect between lugdunin and antibiotics. This study highlights the role of lugdunin in sensitizing energy-compromised\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      to antibiotics, presenting a promising avenue for combating SCV-related infections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The rise of antimicrobial resistance in\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      , particularly small colony variants (SCVs), poses a significant clinical challenge due to their persistence and reduced susceptibility to antibiotics.\n                      <jats:italic toggle=\"yes\">Staphylococcus lugdunensis<\/jats:italic>\n                      produces lugdunin, a potent antimicrobial compound that inhibits\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      growth. This study reveals that energy metabolism-deficient mutants and clinical SCVs exhibit increased susceptibility to lugdunin, underscoring the role of energy metabolism in bacterial defense. Furthermore, lugdunin enhances SCV susceptibility to antibiotics oxacillin and vancomycin, suggesting a potential strategy to overcome antibiotic resistance. By elucidating the link between energy metabolism and susceptibility to antimicrobial compounds, this study highlights lugdunin as a promising candidate for combating SCV-associated infections and antibiotic-resistant\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01006-25","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T12:33:33Z","timestamp":1755866013000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Defects in energy metabolism increase the susceptibility of\n                    <i>Staphylococcus aureus<\/i>\n                    and its small colony variants (SCVs) to\n                    <i>Staphylococcus lugdunensis<\/i>\n                    and lugdunin"],"prefix":"10.1128","volume":"13","author":[{"given":"Chao-Chin","family":"Liu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d80zx46","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/00d80zx46","id-type":"ROR","asserted-by":"publisher"}],"name":"Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5921-7974","authenticated-orcid":true,"given":"Shih-Cheng","family":"Chang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d80zx46","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/00d80zx46","id-type":"ROR","asserted-by":"publisher"}],"name":"Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/02dnn6q67","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Laboratory, Chang Gung Memorial Hospital at Linkou","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jwu-Ching","family":"Shu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d80zx46","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/00d80zx46","id-type":"ROR","asserted-by":"publisher"}],"name":"Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/02dnn6q67","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Laboratory, Chang Gung Memorial Hospital at Linkou","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3498-9377","authenticated-orcid":true,"given":"Mei-Hui","family":"Lin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d80zx46","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/00d80zx46","id-type":"ROR","asserted-by":"publisher"}],"name":"Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University","place":["Taoyuan, Taiwan"]},{"id":[{"id":"https:\/\/ror.org\/02dnn6q67","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical Laboratory, Chang Gung Memorial Hospital at Linkou","place":["Taoyuan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00107"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/499406"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-017-1801-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-021-04315-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0924-8579(99)00170-3"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1384"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18634"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-024-01913-x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.gpp3-0029-2018"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201901589"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00578-24"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47803-6"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00088-10"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00170"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01414"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt395"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2015.05.022"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404728101"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep25233"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.2.687-693.2006"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00976-13"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr900021w"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00069-15"},{"key":"e_1_3_3_25_2","first-page":"201","volume-title":"Molecular medical microbiology","author":"Ward B","year":"2015","unstructured":"Ward B. 2015. Bacterial energy metabolism, p 201\u2013233. In Molecular medical microbiology, 2nd ed. Elsevier, London.","edition":"2"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1509743112"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00659-17"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.756809"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00285-12"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00363"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2022.127040"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00141"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01868942"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00380-13"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.01298-23"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt072"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a026997"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz746"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01734-20"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01006-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01006-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T21:31:02Z","timestamp":1759872662000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.01006-25"}},"subtitle":[],"editor":[{"given":"Kunyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,7]]},"references-count":38,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10,7]]}},"alternative-id":["10.1128\/spectrum.01006-25"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.01006-25","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,7]]},"assertion":[{"value":"2025-04-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01006-25"}}