{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:43:03Z","timestamp":1790991783862,"version":"4.1.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":72,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002385","name":"Egyptian Ministry of Higher Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002385","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The evolution of antimicrobial resistance (AMR) in biofilms has been repeatedly studied by experimental evolution in vitro, but rarely in vivo. The complex microenvironment at the infection site imposes selective pressures on the bacterial biofilms, potentially influencing the development of AMR. We report here the development of AMR in an in vivo mouse model of Pseudomonas aeruginosa biofilm lung infection. The P. aeruginosa embedded in seaweed alginate beads underwent four successive lung infection passages with or without ciprofloxacin (CIP) exposure. The development of CIP resistance was assessed at each passage by population analysis of the bacterial populations recovered from the lungs of CIP-treated and control mice, with subsequent whole-genome sequencing of selected isolates. As inflammation plays a crucial role in shaping the microenvironment at the infection site, its impact was explored through the measurement of cytokine levels in the lung homogenate. A rapid development of AMR was observed starting from the second passage in the CIP-treated mice. Genetic analysis revealed mutations in nfxB, efflux pumps (mexZ), and two-component systems (parS) contribution to CIP resistance. The control group isolates exhibited mutations in the dipA gene, likely associated with biofilm dispersion. In the initial two passages, the CIP-treated group exhibited an elevated inflammatory response compared to the control group. This increase may potentially contribute to the release of mutagenic reactive oxygen species and the development of AMR. In conclusion, this study illustrates the complex relationship between infection, antibiotic treatment, and immune response.<\/jats:p>","DOI":"10.1093\/ismejo\/wrae036","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T20:08:54Z","timestamp":1710360534000},"source":"Crossref","is-referenced-by-count":47,"title":["<i>In vivo<\/i> evolution of antimicrobial resistance in a biofilm model of <i>Pseudomonas aeruginosa<\/i> lung infection"],"prefix":"10.1093","volume":"18","author":[{"given":"Doaa","family":"Higazy","sequence":"first","affiliation":[{"name":"Costerton Biofilm Center , Department of Immunology and Microbiology, , 2200 N Copenhagen , Denmark"},{"name":"University of Copenhagen , Department of Immunology and Microbiology, , 2200 N Copenhagen , Denmark"},{"name":"Department of Microbiology , Faculty of Agriculture, , 12613 Giza , Egypt"},{"name":"Cairo University , Faculty of Agriculture, , 12613 Giza , Egypt"},{"name":"Department of Clinical Microbiology , Rigshospitalet, , 2100 \u00d8 Copenhagen , Denmark"},{"name":"University of Copenhagen , Rigshospitalet, , 2100 \u00d8 Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh Duc","family":"Pham","sequence":"additional","affiliation":[{"name":"Division of Systems Pharmacology & Pharmacy , Leiden Academic Centre for Drug Research, , 2300 RA Leiden , The Netherlands"},{"name":"Leiden University , Leiden Academic Centre for Drug Research, , 2300 RA Leiden , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coen","family":"van Hasselt","sequence":"additional","affiliation":[{"name":"Division of Systems Pharmacology & Pharmacy , Leiden Academic Centre for Drug Research, , 2300 RA Leiden , The Netherlands"},{"name":"Leiden University , Leiden Academic Centre for Drug Research, , 2300 RA Leiden , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"H\u00f8iby","sequence":"additional","affiliation":[{"name":"Costerton Biofilm Center , Department of Immunology and Microbiology, , 2200 N Copenhagen , Denmark"},{"name":"University of Copenhagen , Department of Immunology and Microbiology, , 2200 N Copenhagen , Denmark"},{"name":"Department of Clinical Microbiology , Rigshospitalet, , 2100 \u00d8 Copenhagen , Denmark"},{"name":"University of Copenhagen , Rigshospitalet, , 2100 \u00d8 Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Jelsbak","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biomedicine, Technical University of Denmark , 2800 Kgs. Lyngby , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Moser","sequence":"additional","affiliation":[{"name":"Costerton Biofilm Center , Department of Immunology and Microbiology, , 2200 N Copenhagen , Denmark"},{"name":"University of Copenhagen , Department of Immunology and Microbiology, , 2200 N Copenhagen , Denmark"},{"name":"Department of Clinical Microbiology , Rigshospitalet, , 2100 \u00d8 Copenhagen , Denmark"},{"name":"University of Copenhagen , Rigshospitalet, , 2100 \u00d8 Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Ciofu","sequence":"additional","affiliation":[{"name":"Costerton Biofilm Center , Department of Immunology and Microbiology, , 2200 N Copenhagen , Denmark"},{"name":"University of Copenhagen , Department of Immunology and Microbiology, , 2200 N Copenhagen , 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