TY - JOUR
T1 - Iron homeostasis affects antibiotic-mediated cell death in Pseudomonas species
AU - Yeom, Jinki
AU - Imlay, James A.
AU - Park, Woojun
PY - 2010/7/16
Y1 - 2010/7/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77954609311&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954609311&partnerID=8YFLogxK
U2 - 10.1074/jbc.M110.127456
DO - 10.1074/jbc.M110.127456
M3 - Article
C2 - 20479007
AN - SCOPUS:77954609311
SN - 0021-9258
VL - 285
SP - 22689
EP - 22695
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 29
ER -