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A Drug Repositioning Screening Identified Pentetic Acid as a Potential Therapeutic Agent for Suppressing the Elastase-mediated Virulence of Pseudomonas aeruginosa.
MedLine Citation:
PMID:  25246397     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 pentaacetic 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 as low as 20 μM DTPA. Supplementation with Zn(2+) or Mn(2+) 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 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, 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.
Authors:
Mia Gi; Junhui Jeong; Keehoon Lee; Kang-Mu Lee; Masanori Toyofuku; Dong Eun Yong; Sang Sun Yoon; Jae Young Choi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-22
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  -     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-23     Completed Date:  -     Revised Date:  2014-9-24    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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