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A Drug-Repositioning Screening Identifies Pentetic Acid as a Potential Therapeutic Agent for Suppressing the Elastase-Mediated Virulence of Pseudomonas aeruginosa

DC Field Value Language
dc.contributor.author정준희-
dc.contributor.author최재영-
dc.contributor.author기미아-
dc.contributor.author용동은-
dc.contributor.author윤상선-
dc.contributor.author이강무-
dc.date.accessioned2015-01-06T17:36:31Z-
dc.date.available2015-01-06T17:36:31Z-
dc.date.issued2014-
dc.identifier.issn0066-4804-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/100297-
dc.description.abstractPseudomonas aeruginosa, 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 P. aeruginosa strain PAO1 was significantly decreased when grown with a concentration as low as 20 μM DTPA. Supplementation with Zn2+ or Mn2+ 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 lasB gene and levels of the Pseudomonas quinolone signal (PQS), a molecule that mediates P. aeruginosa 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 P. aeruginosa airway infection.-
dc.description.statementOfResponsibilityopen-
dc.format.extent7205~7214-
dc.relation.isPartOfANTIMICROBIAL AGENTS AND CHEMOTHERAPY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdministration, Intranasal-
dc.subject.MESHAnimals-
dc.subject.MESHAnti-Bacterial Agents/metabolism-
dc.subject.MESHAnti-Bacterial Agents/pharmacology*-
dc.subject.MESHBacterial Proteins/antagonists & inhibitors*-
dc.subject.MESHBacterial Proteins/chemistry-
dc.subject.MESHBacterial Proteins/metabolism-
dc.subject.MESHBiofilms/drug effects-
dc.subject.MESHBiofilms/growth & development-
dc.subject.MESHCations, Divalent-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHDrug Repositioning-
dc.subject.MESHEnzyme Inhibitors/metabolism-
dc.subject.MESHEnzyme Inhibitors/pharmacology*-
dc.subject.MESHHumans-
dc.subject.MESHIron Chelating Agents/metabolism-
dc.subject.MESHIron Chelating Agents/pharmacology-
dc.subject.MESHMale-
dc.subject.MESHManganese/metabolism-
dc.subject.MESHManganese/pharmacology-
dc.subject.MESHMetalloendopeptidases/antagonists & inhibitors*-
dc.subject.MESHMetalloendopeptidases/chemistry-
dc.subject.MESHMetalloendopeptidases/metabolism-
dc.subject.MESHMice-
dc.subject.MESHPentetic Acid/metabolism-
dc.subject.MESHPentetic Acid/pharmacology*-
dc.subject.MESHPseudomonas Infections/drug therapy*-
dc.subject.MESHPseudomonas Infections/microbiology-
dc.subject.MESHPseudomonas aeruginosa/drug effects*-
dc.subject.MESHPseudomonas aeruginosa/enzymology-
dc.subject.MESHPseudomonas aeruginosa/pathogenicity-
dc.subject.MESHQuinolones/metabolism-
dc.subject.MESHQuorum Sensing/drug effects-
dc.subject.MESHSmall Molecule Libraries/metabolism-
dc.subject.MESHSmall Molecule Libraries/pharmacology-
dc.subject.MESHVirulence-
dc.subject.MESHZinc/metabolism-
dc.subject.MESHZinc/pharmacology-
dc.titleA Drug-Repositioning Screening Identifies Pentetic Acid as a Potential Therapeutic Agent for Suppressing the Elastase-Mediated Virulence of Pseudomonas aeruginosa-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentYonsei Biomedical Research Center (연세의생명연구원)-
dc.contributor.googleauthorMia Gi-
dc.contributor.googleauthorJunhui Jeong-
dc.contributor.googleauthorKeehoon Lee-
dc.contributor.googleauthorKang-Mu Lee-
dc.contributor.googleauthorMasanori Toyofuku-
dc.contributor.googleauthorDong Eun Yong-
dc.contributor.googleauthorSang Sun Yoon-
dc.contributor.googleauthorJae Young Choi-
dc.identifier.doi10.1128/AAC.03063-14-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03732-
dc.contributor.localIdA00275-
dc.contributor.localIdA02423-
dc.contributor.localIdA02558-
dc.contributor.localIdA02638-
dc.contributor.localIdA04173-
dc.relation.journalcodeJ00189-
dc.identifier.eissn1098-6596-
dc.identifier.pmid25246397-
dc.identifier.urlhttp://aac.asm.org/content/58/12/7205.long-
dc.contributor.alternativeNameJeong, Jun Hui-
dc.contributor.alternativeNameChoi, Jae Young-
dc.contributor.alternativeNameGi, Mi A-
dc.contributor.alternativeNameYong, Dong Eun-
dc.contributor.alternativeNameYoon, Sang Sun-
dc.contributor.alternativeNameLee, Kang Mu-
dc.contributor.affiliatedAuthorJeong, Jun Hui-
dc.contributor.affiliatedAuthorGi, Mi A-
dc.contributor.affiliatedAuthorYong, Dong Eun-
dc.contributor.affiliatedAuthorYoon, Sang Sun-
dc.contributor.affiliatedAuthorLee, Kang Mu-
dc.contributor.affiliatedAuthorChoi, Jae Young-
dc.rights.accessRightsfree-
dc.citation.volume58-
dc.citation.number12-
dc.citation.startPage7205-
dc.citation.endPage7214-
dc.identifier.bibliographicCitationANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol.58(12) : 7205-7214, 2014-
dc.identifier.rimsid57575-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers

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