Promoting effect of Fe3+ on gentamicin resistance in Escherichia coli
Yi-Feng Huang1, Yi Li1, Jie-Ying Chen1
1Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, MOE Key Laboratory of Tumor Molecular Biology, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, People's Republic of China.
Abstract:
Kinds of antibiotics are used to prevent and control bacteria infections, unfortunately, the overuse and misuse of antibiotic have promoted the emergence and spread of antibiotic-resistant bacteria. Therefore, understanding the mechanism of antibiotic resistance is very important. This study explores the combined effection of metal ions and antibiotic to the drug resistance of Escherichia coli. Our results found that the minimum inhibitory concentration (MIC) increased as the ammonium ferric citrate concentration increased, especially for gentamicin antibiotic. When the Fe3+ concentration reached 300 μM, the survival of E. coli was stably restored with the increased gentamicin concentration. Exogenous Fe3+ could decrease intracellular gentamicin concentration. On the other hand, Fe3+ treatment together with gentamicin could reduce reactive oxygen species (ROS) production, characterized by decreased levels of NADH and ATP. Furthermore, ROS-scavenging enzymes of superoxide dismutase (SOD) and catalase (CAT) were up-regulated and H2O2 plus gentamicin-mediated killing was restored by Fe3+. These results may have significant implications in understanding bacterial antibiotic-resistant mechanisms based on the external Fe3+ concentration.
Insights
Iron ions (Fe3+) can reverse antibiotic resistance in E. coli by affecting drug concentration and reducing oxidative stress. This finding is crucial for understanding bacterial antibiotic resistance mechanisms.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Antibiotic resistance is a growing global health threat driven by overuse and misuse of antibiotics.
- Understanding the mechanisms of antibiotic resistance is crucial for developing effective treatment strategies.
Purpose of the Study:
- To investigate the combined effects of metal ions, specifically iron (Fe3+), and antibiotics on the drug resistance of Escherichia coli.
- To elucidate the mechanisms by which Fe3+ influences antibiotic resistance in E. coli.
Main Methods:
- Determining the minimum inhibitory concentration (MIC) of gentamicin in the presence of varying ammonium ferric citrate concentrations.
- Measuring intracellular gentamicin concentration in E. coli treated with Fe3+ and gentamicin.
- Assessing reactive oxygen species (ROS) production, NADH, and ATP levels.
- Analyzing the expression of ROS-scavenging enzymes superoxide dismutase (SOD) and catalase (CAT).
Main Results:
- Increased ammonium ferric citrate concentration led to a higher MIC for gentamicin against E. coli.
- Fe3+ treatment reduced intracellular gentamicin concentration and restored E. coli survival at higher gentamicin concentrations.
- Fe3+ diminished ROS production, decreased NADH and ATP levels, and up-regulated SOD and CAT enzymes.
- Fe3+ restored the efficacy of H2O2 and gentamicin-mediated killing.
Conclusions:
- External Fe3+ concentration significantly impacts bacterial antibiotic resistance.
- Fe3+ influences antibiotic resistance by altering intracellular drug accumulation and modulating oxidative stress pathways.
- These findings offer insights into bacterial resistance mechanisms and potential strategies to combat antibiotic resistance.
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