{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T22:02:02Z","timestamp":1791756122282,"version":"4.3.4"},"reference-count":80,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"7","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,2,14]]},"abstract":"<jats:p>\n            Individuals with diabetes mellitus frequently develop severe skin and soft tissue infections (SSTIs) that are recalcitrant to antibiotic treatment. We examined how diabetes affects the emergence of antibiotic resistance in a\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            SSTI. We determined that\n            <jats:italic>S. aureus<\/jats:italic>\n            evolves antibiotic resistance rapidly in diabetic mice, while resistance did not occur in nondiabetic mice over the course of infection. Diabetes-associated immune cell dysfunction plays a minor role in the emergence of resistance, while hyperglycemia plays a dominant role facilitating the expansion and takeover of resistant mutants in diabetic infections. Furthermore, vancomycin intermediate resistant isolates display a pronounced fitness defect in nondiabetic mice but not in diabetic mice. Together, these data suggest that the diabetic infection environment represents an ideal reservoir for the emergence and proliferation of antibiotic resistance. Controlling the blood sugar of diabetic mice with insulin resulted in significantly decreased incidence of antibiotic-resistant\n            <jats:italic>S. aureus<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1126\/sciadv.ads1591","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T18:58:36Z","timestamp":1739386716000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":40,"title":["Diabetes potentiates the emergence and expansion of antibiotic resistance"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6949-8634","authenticated-orcid":true,"given":"John C.","family":"Shook","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9044-964X","authenticated-orcid":true,"given":"Christopher J.","family":"Genito","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0936-384X","authenticated-orcid":true,"given":"Benjamin P.","family":"Darwitz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7415-2405","authenticated-orcid":true,"given":"Kaleb J.","family":"Tyson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Z.","family":"Velez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6055-5175","authenticated-orcid":true,"given":"Sophia K.","family":"Bridwell","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Marquette University, Milwaukee, WI 53233, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua B.","family":"Parsons","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."},{"name":"Division of Infectious Diseases, Duke University School of Medicine, Durham, NC 27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-359X","authenticated-orcid":true,"given":"Sarah E.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6669-3231","authenticated-orcid":true,"given":"Christopher W.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Marquette University, Milwaukee, WI 53233, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2155-8375","authenticated-orcid":true,"given":"Brian P.","family":"Conlon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."},{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1839-2922","authenticated-orcid":true,"given":"Lance R.","family":"Thurlow","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."},{"name":"Department of Biomedical Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-71908-9"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109118"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4103\/ajm.ajm_53_20"},{"key":"e_1_3_2_5_2","unstructured":"CDC. Your immune system and diabetes (2023); https:\/\/cdc.gov\/diabetes\/diabetes-complications\/diabetes-immune-system.html?CDC_AAref_Val=https:\/\/cdc.gov\/diabetes\/library\/features\/diabetes_immune_system.html."},{"key":"e_1_3_2_6_2","first-page":"803","article-title":"Identification and characterization of a high vancomycin-resistant Staphylococcus aureus harboring VanA gene cluster isolated from diabetic foot ulcer","volume":"15","author":"Dezfulian A.","year":"2012","unstructured":"A. Dezfulian, M. M. Aslani, M. Oskoui, P. Farrokh, M. Azimirad, H. Dabiri, M. T. Salehian, M. R. Zali, Identification and characterization of a high vancomycin-resistant Staphylococcus aureus harboring VanA gene cluster isolated from diabetic foot ulcer. Iran. J. Basic Med. Sci. 15, 803\u2013806 (2012).","journal-title":"Iran. J. Basic Med. Sci."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000446-200211000-00015"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.2005.25.7.963"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.94253"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10101241"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2021.559595"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02299-23"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1276357"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-2131"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc5569"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13537"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"e0211481","DOI":"10.1371\/journal.pone.0211481","article-title":"Disparities in outcomes of patients admitted with diabetic foot infections","volume":"14","author":"Tan T. W.","year":"2019","unstructured":"T. W. Tan, C. D. Shih, K. C. Concha-Moore, M. M. Diri, B. Hu, D. Marrero, W. Zhou, D. G. Armstrong, Disparities in outcomes of patients admitted with diabetic foot infections. PLOS ONE 14, e0211481 (2019).","journal-title":"PLOS ONE"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/511036"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2020.10.007"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.46.2.S58"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcy235"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.07.001"},{"key":"e_1_3_2_23_2","unstructured":"CDC. (National Diabetes Statistics Report https:\/\/www.cdc.gov\/diabetes\/php\/data-research\/?CDC_AAref_Val=https:\/\/www.cdc.gov\/diabetes\/data\/statstics-report\/index.html 2022) vol. 2023."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00862-24"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add3221"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.10.2904"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023633"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx048"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/jech-2020-216029"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_3_2_31_2","unstructured":"O. B. Jonas I. Alec F. C. J. Berthe F. G. Le Gall P. V. Marquez. Drug-resistant infections:A threat to our economic future. Final report (English). (HNP\/Agriculture Global Antimicrobial Resistance Initiative World Bank Group The World Bank 2017) vol. 2."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2008.12.003"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-022-01126-8"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S243732"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.10.2590"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/42701"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219574110"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003794"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/47.5.647"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00296-16"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00042-13"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004205"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.914512"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41540-019-0122-3"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2019.10.005"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00509-23"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S393415"},{"key":"e_1_3_2_48_2","first-page":"269","article-title":"Vancomycin resistance in Staphylococcus aureus","volume":"90","author":"McGuinness W. A.","year":"2017","unstructured":"W. A. McGuinness, N. Malachowa, F. R. DeLeo, Vancomycin resistance in Staphylococcus aureus. Yale J. Biol. Med. 90, 269\u2013281 (2017).","journal-title":"Yale J. Biol. Med."},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199902183400704"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199902183400701"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/42.2.199"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2008.00104.x"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.11764"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68834"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01073-08"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1086\/675283"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00889-13"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir308"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0287"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz358"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-0138"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.13006"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-022-01357-2"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.00480-22"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00172"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2020.03.004"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0627-y"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)33294-4"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3687"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2003.12.043"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1086\/511041"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/zxaa036"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609839104"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(98)00149-1"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1998.85.5.1708"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00537-12"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_3_2_78_2","doi-asserted-by":"crossref","unstructured":"D. E. Deatherage J. E. Barrick Engineering and Analyzing Multicellular Systems: Methods and Protocols L. Sun W. Shou Eds. (Springer 2014) pp. 165\u20131e88.","DOI":"10.1007\/978-1-4939-0554-6_12"},{"key":"e_1_3_2_79_2","unstructured":"H. Wickham Elegant Graphics for Data Analysis. (Springer-Verlag 2016)."},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00045-15"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011531"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.ads1591","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T10:30:17Z","timestamp":1744885817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.ads1591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,14]]},"references-count":80,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,2,14]]}},"alternative-id":["10.1126\/sciadv.ads1591"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.ads1591","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,14]]},"assertion":[{"value":"2024-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eads1591"}}