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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,12,20]]},"abstract":"<jats:p>\n                    A hallmark of microbial ecology is that interactions between members of a community shape community function. This includes microbial communities in human infections, such as chronic wounds, where interactions can result in more severe diseases.\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    is the most common organism isolated from human chronic wound infections and has been shown to have both cooperative and competitive interactions with\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    . Still, despite considerable study, most interactions between these microbes have been characterized using in\u00a0vitro well-mixed systems, which do not recapitulate the infection environment. Here, we characterized interactions between\n                    <jats:italic>S. aureus<\/jats:italic>\n                    and\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    in chronic murine wounds, focusing on the role that both macro- and micro-scale spatial structures play in disease. We discovered that\n                    <jats:italic>S. aureus<\/jats:italic>\n                    and\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    coexist at high cell densities in murine wounds. High-resolution imaging revealed that these microbes establish a patchy distribution, only occupying 5 to 25% of the wound volume. Using a quantitative framework, we identified a precise spatial structure at both the macro (mm)- and micro (\u00b5m)-scales, which was largely mediated by\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    production of the antimicrobial 2-heptyl-4-hydroxyquinoline N-oxide, while the antimicrobial pyocyanin had no impact. Finally, we discovered that this precise spatial structure enhances\n                    <jats:italic>S. aureus<\/jats:italic>\n                    tolerance to aminoglycoside antibiotics but not vancomycin. Our results provide mechanistic insights into the biogeography of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    and\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    coinfected wounds and implicate spatial structure as a key determinant of antimicrobial tolerance in wound infections.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2212340119","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T13:15:14Z","timestamp":1671110114000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":54,"title":["Precise spatial structure impacts antimicrobial susceptibility of\n                    <i>S. aureus<\/i>\n                    in polymicrobial wound infections"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1696-1952","authenticated-orcid":false,"given":"Carolyn B.","family":"Ibberson","sequence":"first","affiliation":[{"name":"School of Biological Sciences and Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Emory-Children\u2019s Cystic Fibrosis Center, Atlanta, GA 30310"},{"name":"Department of Microbiology and Plant Biology, University of Oklahoma, Norman, OK 73019"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7057-2598","authenticated-orcid":false,"given":"Juan P.","family":"Barraza","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Emory-Children\u2019s Cystic Fibrosis Center, Atlanta, GA 30310"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4942-6614","authenticated-orcid":false,"given":"Avery L.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Plant Biology, University of Oklahoma, Norman, OK 73019"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengbo","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Emory-Children\u2019s Cystic Fibrosis Center, Atlanta, GA 30310"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin","family":"Whiteley","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Emory-Children\u2019s Cystic Fibrosis Center, Atlanta, GA 30310"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)70155-0"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2013.06.002"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-481X.2006.00159.x"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12275-014-4067-3"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00013-11"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122688"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2012.04001.x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix621"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2017.79"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1214550110"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.2.554-566.2005"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02880"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","unstructured":"J. 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Deposited 12 July 2022."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2212340119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T08:36:12Z","timestamp":1695285372000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2212340119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,15]]},"references-count":67,"journal-issue":{"issue":"51","published-print":{"date-parts":[[2022,12,20]]}},"alternative-id":["10.1073\/pnas.2212340119"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2212340119","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,15]]},"assertion":[{"value":"2022-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2212340119"}}