{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:19:23Z","timestamp":1785403163587,"version":"3.56.0"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI173004, R21AI14088"],"award-info":[{"award-number":["R01AI173004, R21AI14088"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2025,11,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Individuals with poorly controlled diabetes mellitus often develop multispecies skin and soft tissue infections, with\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      among the most prevalent bacteria isolated from infection sites worldwide. Diabetic infections are recalcitrant to conventional antibiotic regimens and may be a reservoir for emergent antibiotic-resistant bacterial strains. Supporting this, we have previously shown that rifampicin treatment elicits the emergence and expansion of rifampicin-resistant (Rif-r)\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      only in diabetic mice, potentially due to greater bacterial outgrowth increasing the frequency of resistance-conferring mutations. However, whether\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      exhibits altered resistance outcomes during multispecies diabetic infections is unclear. During co-infection with\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      under normoglycemic conditions,\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      exhibits reduced growth and altered susceptibility to several antibiotics. In contrast, we previously observed that glucose availability allows\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      to largely overcome\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      -mediated growth inhibition. Here, we explored\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      resistance outcomes under hyperglycemic conditions in the context of co-infection with\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      during antibiotic challenge. We found that\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      exoproducts regulated by the\n                      <jats:italic toggle=\"yes\">Pseudomonas<\/jats:italic>\n                      quinolone signal quorum sensing system inhibit the emergence but not the expansion of Rif-r\n                      <jats:italic toggle=\"yes\">S. aureus in vitro<\/jats:italic>\n                      under glucose-replete conditions. In contrast, we recovered equivalent Rif-r\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      burdens from diabetic mice during mono- and co-infection with\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      . These results demonstrate that the diabetic infection microenvironment is conducive to emergent Rif-r\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      despite external pressures elicited by\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Poorly controlled diabetes mellitus confers an increased susceptibility to bacterial infections, with\n                        <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                        frequently isolated from diabetic skin wounds.\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        readily develops antibiotic resistance during diabetic mono-infection under antibiotic pressure, but whether this occurs during diabetic co-infection is unclear. Under normoglycemic conditions, secreted\n                        <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                        factors alter\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        tolerance to several antibiotics. Here, we show that these\n                        <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                        exoproducts further inhibit the emergence of antibiotic-resistant\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        regardless of glucose availability\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        , but this does not occur during subcutaneous co-infection in diabetic mice. These results provide initial insights regarding conditions that may inhibit\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        resistance development in hyperglycemic environments but underscore the influence of the host infection microenvironment in shaping resistance outcomes.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00333-25","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T13:00:11Z","timestamp":1760619611000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>Pseudomonas aeruginosa<\/i>\n                    differentially influences antibiotic-resistant\n                    <i>Staphylococcus aureus<\/i>\n                    emergence and expansion in hyperglycemic environments"],"prefix":"10.1128","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0936-384X","authenticated-orcid":true,"given":"Benjamin P.","family":"Darwitz","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill","place":["Chapel Hill, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary J.","family":"Lifschin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill","place":["Chapel Hill, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire M.","family":"Miller","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill","place":["Chapel Hill, 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":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill","place":["Chapel Hill, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casei A.","family":"Gossett","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill","place":["Chapel Hill, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyla E.","family":"Augustine","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill","place":["Chapel Hill, 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":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill","place":["Chapel Hill, USA"]},{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill","place":["Chapel Hill, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2174\/1573399815666191024085838"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.2.510"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00509-23"},{"key":"e_1_3_3_5_2","first-page":"1","volume-title":"Endotext","author":"Nagendra L","year":"2022","unstructured":"Nagendra L, Boro H, Mannar V, Purnell J, Sahay R. 2022. 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