{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:29:16Z","timestamp":1790389756319,"version":"4.1.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>, a Gram-negative bacterium of clinical significance, produces elastase as a predominant exoprotease. Here, we screened a library of chemical compounds currently used for human medication and identified diethylene triamine penta-acetic acid (DTPA, pentetic acid) as an agent that suppresses the production of elastase. Elastase activity found in the prototype<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>strain PAO1 was significantly decreased when grown with a concentration as low as 20 \u03bcM DTPA. Supplementation with Zn<jats:sup>2+<\/jats:sup>or Mn<jats:sup>2+<\/jats:sup>ions restored the suppressive effect of DTPA, suggesting that the DTPA-mediated decrease in elastase activity is associated with ion-chelating activity. In DTPA-treated PAO1 cells, transcription of the elastase-encoding<jats:italic>lasB<\/jats:italic>gene and levels of the<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas<\/jats:named-content>quinolone signal (PQS), a molecule that mediates<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>quorum sensing (QS), were significantly downregulated, reflecting the potential involvement of the PQS QS system in DTPA-mediated elastase suppression. Biofilm formation was also decreased by DTPA treatment. When A549 alveolar type II-like adenocarcinoma cells were infected with PAO1 cells in the presence of DTPA, A549 cell viability was substantially increased. Furthermore, the intranasal delivery of DTPA to PAO1-infected mice alleviated the pathogenic effects of PAO1 cells in the animals. Together, our results revealed a novel function for a known molecule that may help treat<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. aeruginosa<\/jats:named-content>airway infection.<\/jats:p>","DOI":"10.1128\/aac.03063-14","type":"journal-article","created":{"date-parts":[[2014,9,23]],"date-time":"2014-09-23T05:05:57Z","timestamp":1411448757000},"page":"7205-7214","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["A Drug-Repositioning Screening Identifies Pentetic Acid as a Potential Therapeutic Agent for Suppressing the Elastase-Mediated Virulence of Pseudomonas aeruginosa"],"prefix":"10.1128","volume":"58","author":[{"given":"Mia","family":"Gi","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Brain Korea 21 PLUS Project for Medical Science, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Brain Korea 21 PLUS Project for Medical Science, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keehoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brain Korea 21 PLUS Project for Medical Science, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang-Mu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brain Korea 21 PLUS Project for Medical Science, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Toyofuku","sequence":"additional","affiliation":[{"name":"Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Eun","family":"Yong","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Sun","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Brain Korea 21 PLUS Project for Medical Science, Seoul, South Korea"},{"name":"Institute for Immunology and Immunological Diseases, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Brain Korea 21 PLUS Project for Medical Science, Seoul, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1104650"},{"key":"e_1_3_2_3_2","first-page":"333","article-title":"Clinical studies of nosocomial infection. 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