Iron homeostasis affects antibiotic-mediated cell death in Pseudomonas species.
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.
Yeom
Jinki
J
Division of Environmental Science and Ecological Engineering, Korea University, Seoul, 136-713, South Korea.
Imlay
James A
JA
Park
Woojun
W
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D004249:DNA Damage; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects* / Q000235:genetics; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D018384:Oxidative Stress / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000166:cytology* / Q000187:drug effects / Q000235:genetics; D016958:Pseudomonas putida / Q000166:cytology* / Q000187:drug effects / Q000235:genetics; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics
D000900:Anti-Bacterial Agents; D015415:Biomarkers; D007501:Iron