{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:11:39Z","timestamp":1775841099004,"version":"3.50.1"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | NIH | NIAID | Division of Intramural Research, National Institute of Allergy and Infectious Diseases","award":["1R21AI151615"],"award-info":[{"award-number":["1R21AI151615"]}]},{"name":"DHAC | National Health and Medical Research Council","award":["APP 1183640"],"award-info":[{"award-number":["APP 1183640"]}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["WOLFGA19G0"],"award-info":[{"award-number":["WOLFGA19G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2023,12,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Diabetes is associated with several health consequences, including increased susceptibility to more frequent and severe infections. Bacterial infections associated with diabetes are typically polymicrobial, with\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            and\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            frequently isolated from the same infection site.\n            <jats:italic>S. aureus<\/jats:italic>\n            and\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            are frequently found in diabetic skin and soft tissue infections, in the lungs of people with cystic fibrosis, and in indwelling device infections. Numerous studies have investigated interactions between these two pathogens primarily using\n            <jats:italic>in vitro<\/jats:italic>\n            systems. These models have several limitations as they do not accurately reflect the complexities of an immune response nor the nutrient dynamics in a diabetic infection microenvironment. Here, we describe a novel murine indwelling device co-infection model that allows us to study the interactions between\n            <jats:italic>S. aureus<\/jats:italic>\n            and\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            within the context of an immune response during both normal and diabetic infections. Our data shows that\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            significantly inhibits\n            <jats:italic>S. aureus<\/jats:italic>\n            growth during co-infection in a normal mouse and that inhibition is not dependent on the\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            PQS quorum sensing system. Conversely, in a diabetic co-infection,\n            <jats:italic>S. aureus<\/jats:italic>\n            overcomes inhibition by\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            and this phenotype is reliant on\n            <jats:italic>S. aureus<\/jats:italic>\n            glycolysis. We also demonstrate that both organisms display increased virulence potential in a diabetic co-infection as we observe increased dissemination to peripheral tissues. This study revealed novel\n            <jats:italic>in vivo<\/jats:italic>\n            interactions between\n            <jats:italic>S. aureus<\/jats:italic>\n            and\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            and advances our understanding of the complex interactions between microorganisms in polymicrobial infections in clinically relevant infection microenvironments.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Individuals with diabetes are prone to more frequent and severe infections, with many of these infections being polymicrobial. Polymicrobial infections are frequently observed in skin infections and in individuals with cystic fibrosis, as well as in indwelling device infections. Two bacteria frequently co-isolated from infections are\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              and\n              <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n              . Several studies have examined the interactions between these microorganisms. The majority of these studies use\n              <jats:italic>in vitro<\/jats:italic>\n              model systems that cannot accurately replicate the microenvironment of diabetic infections. We employed a novel murine indwelling device model to examine interactions between\n              <jats:italic>S. aureus<\/jats:italic>\n              and\n              <jats:italic>P. aeruginosa<\/jats:italic>\n              . Our data show that competition between these bacteria results in reduced growth in a normal infection. In a diabetic infection, we observe increased growth of both microbes and more severe infection as both bacteria invade surrounding tissues. Our results demonstrate that diabetes changes the interaction between bacteria resulting in poor infection outcomes.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.02299-23","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:54:35Z","timestamp":1699365275000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Hyperglycemia potentiates increased\n            <i>Staphylococcus aureus<\/i>\n            virulence and resistance to growth inhibition by\n            <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","volume":"11","author":[{"given":"Christopher J.","family":"Genito","sequence":"first","affiliation":[{"name":"Division of Oral and Craniofacial Health Sciences, University of North Carolina at Chapel Hill Adams School of Dentistry , Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin P.","family":"Darwitz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine , Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4765-2738","authenticated-orcid":false,"given":"Matthew A.","family":"Greenwald","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine , Chapel Hill, North Carolina, USA"},{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill School of Medicine , Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew C.","family":"Wolfgang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine , Chapel Hill, North Carolina, USA"},{"name":"Marsico Lung Institute, University of North Carolina at Chapel Hill School of Medicine , Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1839-2922","authenticated-orcid":true,"given":"Lance R.","family":"Thurlow","sequence":"additional","affiliation":[{"name":"Division of Oral and Craniofacial Health Sciences, University of North Carolina at Chapel Hill Adams School of Dentistry , Chapel Hill, North Carolina, USA"},{"name":"Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine , Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"2022. National diabetes statistics report | Diabetes. CDC. Available from: https:\/\/www.cdc.gov\/diabetes\/data\/statistics-report\/index.html. 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