Cited 31 times in
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.author | 정준희 | - |
dc.contributor.author | 최재영 | - |
dc.contributor.author | 기미아 | - |
dc.contributor.author | 용동은 | - |
dc.contributor.author | 윤상선 | - |
dc.contributor.author | 이강무 | - |
dc.date.accessioned | 2015-01-06T17:36:31Z | - |
dc.date.available | 2015-01-06T17:36:31Z | - |
dc.date.issued | 2014 | - |
dc.identifier.issn | 0066-4804 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/100297 | - |
dc.description.abstract | Pseudomonas 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.statementOfResponsibility | open | - |
dc.format.extent | 7205~7214 | - |
dc.relation.isPartOf | ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Administration, Intranasal | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Anti-Bacterial Agents/metabolism | - |
dc.subject.MESH | Anti-Bacterial Agents/pharmacology* | - |
dc.subject.MESH | Bacterial Proteins/antagonists & inhibitors* | - |
dc.subject.MESH | Bacterial Proteins/chemistry | - |
dc.subject.MESH | Bacterial Proteins/metabolism | - |
dc.subject.MESH | Biofilms/drug effects | - |
dc.subject.MESH | Biofilms/growth & development | - |
dc.subject.MESH | Cations, Divalent | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Drug Repositioning | - |
dc.subject.MESH | Enzyme Inhibitors/metabolism | - |
dc.subject.MESH | Enzyme Inhibitors/pharmacology* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Iron Chelating Agents/metabolism | - |
dc.subject.MESH | Iron Chelating Agents/pharmacology | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Manganese/metabolism | - |
dc.subject.MESH | Manganese/pharmacology | - |
dc.subject.MESH | Metalloendopeptidases/antagonists & inhibitors* | - |
dc.subject.MESH | Metalloendopeptidases/chemistry | - |
dc.subject.MESH | Metalloendopeptidases/metabolism | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Pentetic Acid/metabolism | - |
dc.subject.MESH | Pentetic Acid/pharmacology* | - |
dc.subject.MESH | Pseudomonas Infections/drug therapy* | - |
dc.subject.MESH | Pseudomonas Infections/microbiology | - |
dc.subject.MESH | Pseudomonas aeruginosa/drug effects* | - |
dc.subject.MESH | Pseudomonas aeruginosa/enzymology | - |
dc.subject.MESH | Pseudomonas aeruginosa/pathogenicity | - |
dc.subject.MESH | Quinolones/metabolism | - |
dc.subject.MESH | Quorum Sensing/drug effects | - |
dc.subject.MESH | Small Molecule Libraries/metabolism | - |
dc.subject.MESH | Small Molecule Libraries/pharmacology | - |
dc.subject.MESH | Virulence | - |
dc.subject.MESH | Zinc/metabolism | - |
dc.subject.MESH | Zinc/pharmacology | - |
dc.title | A Drug-Repositioning Screening Identifies Pentetic Acid as a Potential Therapeutic Agent for Suppressing the Elastase-Mediated Virulence of Pseudomonas aeruginosa | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Yonsei Biomedical Research Center (연세의생명연구원) | - |
dc.contributor.googleauthor | Mia Gi | - |
dc.contributor.googleauthor | Junhui Jeong | - |
dc.contributor.googleauthor | Keehoon Lee | - |
dc.contributor.googleauthor | Kang-Mu Lee | - |
dc.contributor.googleauthor | Masanori Toyofuku | - |
dc.contributor.googleauthor | Dong Eun Yong | - |
dc.contributor.googleauthor | Sang Sun Yoon | - |
dc.contributor.googleauthor | Jae Young Choi | - |
dc.identifier.doi | 10.1128/AAC.03063-14 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A03732 | - |
dc.contributor.localId | A00275 | - |
dc.contributor.localId | A02423 | - |
dc.contributor.localId | A02558 | - |
dc.contributor.localId | A02638 | - |
dc.contributor.localId | A04173 | - |
dc.relation.journalcode | J00189 | - |
dc.identifier.eissn | 1098-6596 | - |
dc.identifier.pmid | 25246397 | - |
dc.identifier.url | http://aac.asm.org/content/58/12/7205.long | - |
dc.contributor.alternativeName | Jeong, Jun Hui | - |
dc.contributor.alternativeName | Choi, Jae Young | - |
dc.contributor.alternativeName | Gi, Mi A | - |
dc.contributor.alternativeName | Yong, Dong Eun | - |
dc.contributor.alternativeName | Yoon, Sang Sun | - |
dc.contributor.alternativeName | Lee, Kang Mu | - |
dc.contributor.affiliatedAuthor | Jeong, Jun Hui | - |
dc.contributor.affiliatedAuthor | Gi, Mi A | - |
dc.contributor.affiliatedAuthor | Yong, Dong Eun | - |
dc.contributor.affiliatedAuthor | Yoon, Sang Sun | - |
dc.contributor.affiliatedAuthor | Lee, Kang Mu | - |
dc.contributor.affiliatedAuthor | Choi, Jae Young | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 58 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 7205 | - |
dc.citation.endPage | 7214 | - |
dc.identifier.bibliographicCitation | ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol.58(12) : 7205-7214, 2014 | - |
dc.identifier.rimsid | 57575 | - |
dc.type.rims | ART | - |
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