Document Detail

Iron homeostasis affects antibiotic-mediated cell death in Pseudomonas species.
MedLine Citation:
PMID:  20479007     Owner:  NLM     Status:  MEDLINE    
Antibiotics can induce cell death via a variety of action modes, including the inhibition of transcription, ribosomal function, and cell wall biosynthesis. In this study, we demonstrated directly that iron availability is important to the action of antibiotics, and the ferric reductases of Pseudomonas putida and Pseudomonas aeruginosa could accelerate antibiotic-mediated cell death by promoting the Fenton reaction. The modulation of reduced nicotinamide-adenine dinucleotide (NADH) levels and iron chelation affected the actions of antibiotics. Interestingly, the deletion of the ferric reductase gene confers more antibiotic resistance upon cells, and its overexpression accelerates antibiotic-mediated cell death. The results of transcriptome analysis showed that both Pseudomonas species induce many oxidative stress genes under antibiotic conditions, which could not be observed in ferric reductase mutants. Our results indicate that iron homeostasis is crucial for bacterial cell survival under antibiotics and should constitute a significant target for boosting the action of antibiotics.
Jinki Yeom; James A Imlay; Woojun Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-17
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-12     Completed Date:  2010-08-06     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  22689-95     Citation Subset:  IM    
Division of Environmental Science and Ecological Engineering, Korea University, Seoul, 136-713, South Korea.
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MeSH Terms
Anti-Bacterial Agents / pharmacology*
Biological Markers / metabolism
DNA Damage
Gene Expression Profiling
Gene Expression Regulation, Bacterial / drug effects
Homeostasis / drug effects*,  genetics
Intracellular Space / drug effects,  metabolism
Iron / metabolism*
Microbial Sensitivity Tests
Microbial Viability / drug effects*
Oxidative Stress / genetics
Pseudomonas aeruginosa / cytology*,  drug effects,  genetics
Pseudomonas putida / cytology*,  drug effects,  genetics
Stress, Physiological / drug effects,  genetics
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Biological Markers; 7439-89-6/Iron

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