{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:06:30Z","timestamp":1792181190122,"version":"4.4.0"},"reference-count":38,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Sygeforsikringen Danmark","award":["2021-0300"],"award-info":[{"award-number":["2021-0300"]}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"crossref","award":["NNF18SA0034966"],"award-info":[{"award-number":["NNF18SA0034966"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Danish Innovation Foundation","award":["0161-00003"],"award-info":[{"award-number":["0161-00003"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Persistent urinary tract infections (UTIs) in hospitalized patients constitute an important medical problem. It is estimated that 75% of nosocomial UTIs are associated with urinary tract catheters with\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      being a species that forms biofilms on these catheters. These infections are highly resistant to standard-of-care antibiotics, and the effects of the host immune defenses, which allows for development of persistent infections. With antibiotics losing their efficacy, new treatment options against resilient infections, such as catheter-associated urinary tract infections (CAUTIs), are critically needed. Central to our anti-biofilm approach is the manipulation of the c-di-GMP signaling pathway in\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      to switch bacteria from the protective biofilm to the unprotected planktonic mode of life. We recently identified a compound (H6-335-P1), that stimulates the c-di-GMP degrading activity of the\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      BifA protein which plummets the intracellular c-di-GMP content and induces dispersal of\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      biofilm bacteria into the planktonic state. In the present study, we formulated H6-335-P1 as a hydrochloride salt (Disperazol), which is water-soluble and facilitates delivery via injection or oral administration. Disperazol can work as a monotherapy, but we observed a 100-fold improvement in efficacy when treating murine\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      CAUTIs with a Disperazol\/ciprofloxacin combination. Biologically active Disperazol reached the bladder 30 min after oral administration. Our study provides proof of concept that Disperazol can be used in combination with a relevant antibiotic for effective treatment of CAUTIs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01481-23","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T08:28:26Z","timestamp":1715156906000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["High efficacy treatment of murine\n                    <i>Pseudomonas aeruginosa<\/i>\n                    catheter-associated urinary tract infections using the c-di-GMP modulating anti-biofilm compound Disperazol in combination with ciprofloxacin"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0256-892X","authenticated-orcid":true,"given":"Louise Dahl","family":"Hultqvist","sequence":"first","affiliation":[{"name":"Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens Bo","family":"Andersen","sequence":"additional","affiliation":[{"name":"Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl Martin","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte Uldahl","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Technical University of Denmark, Lyngby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Rybtke","sequence":"additional","affiliation":[{"name":"Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1671-2155","authenticated-orcid":true,"given":"Tim Holm","family":"Jakobsen","sequence":"additional","affiliation":[{"name":"Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Eiland","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Qvortrup","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, CFIM, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Moser","sequence":"additional","affiliation":[{"name":"Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Graz","sequence":"additional","affiliation":[{"name":"Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrine","family":"Qvortrup","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Technical University of Denmark, Lyngby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9751-474X","authenticated-orcid":true,"given":"Tim","family":"Tolker-Nielsen","sequence":"additional","affiliation":[{"name":"Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5004-8609","authenticated-orcid":true,"given":"Michael","family":"Givskov","sequence":"additional","affiliation":[{"name":"Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 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Guideline for prevention of catheter- associated urinary tract infections. Center for Disease Control and Prevention. 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