Ferric chloride induces ferroptosis in Pseudomonas aeruginosa and heals wound infection in a mouse model
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Updated: Aug 6, 2025
A Delayed Inoculation Model of Chronic Pseudomonas aeruginosa Wound Infection
Published on: February 20, 2020
Minmin Huang1, Zhen Wang1, Lishan Yao1
1School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an, 710021, China.
Background:
Pseudomonas aeruginosa is one of the most common pathogens that lead to fatal human infection. This Gram-negative pathogen has evolved complex drug resistance, which poses significant challenges to the current antibiotic-dependent healthcare system. New therapeutic approaches are urgently required to treat infections caused by P. aeruginosa.
Methods:
Inspired by ferroptosis, the antibacterial effects of iron compounds on P. aeruginosa via direct exposure were investigated. In addition, thermal-responsive hydrogels to carry FeCl3 were developed as a wound dressing to treat P. aeruginosa-induced wound infection in a mouse model.
Results:
The results showed that 200 µM FeCl3 killed more than 99.9% of P. aeruginosa cells. FeCl3-mediated cell death in P. aeruginosa was associated with hallmarks of ferroptosis in mammalian cells, including reactive oxygen species (ROS) burst, lipid peroxidation, and DNA damage. Catalase or Fe2+ chelator alleviated FeCl3-mediated cell death, indicating that H2O2 and labile Fe2+ induced the Fenton reaction leading to cell death. Further proteomics analysis showed that proteins related to glutathione (GSH) synthesis and the glutathione peroxidase (GPX) family were significantly downregulated after FeCl3 treatment, which is equivalent to GPX4 inactivation in mammalian cells. The therapeutic effect of FeCl3 on P. aeruginosa was further evaluated in a mouse wound infection model using polyvinyl alcohol-boric acid (PB) hydrogels as a carrier of FeCl3. FeCl3-PB hydrogels completely cleared pus on wounds and promoted wound healing.
Conclusion:
These results indicated that FeCl3 induces microbial ferroptosis in P. aeruginosa and has high therapeutic potential for the treatment of P. aeruginosa wound infection.
Insights
Iron compounds like ferric chloride (FeCl3) can induce microbial ferroptosis in Pseudomonas aeruginosa, offering a novel therapeutic strategy. This approach effectively treats wound infections by clearing bacteria and promoting healing.
Area of Science:
- Biochemistry
- Microbiology
- Materials Science
Background:
- Pseudomonas aeruginosa is a common pathogen causing fatal infections.
- Drug resistance in P. aeruginosa presents a significant healthcare challenge.
- Novel therapeutic strategies are needed to combat P. aeruginosa infections.
Purpose of the Study:
- Investigate the antibacterial effects of iron compounds on P. aeruginosa.
- Explore iron-induced ferroptosis as a mechanism for bacterial cell death.
- Develop a hydrogel-based wound dressing for P. aeruginosa infections.
Main Methods:
- Direct exposure of P. aeruginosa to ferric chloride (FeCl3).
- Development of thermal-responsive hydrogels carrying FeCl3 for wound dressing.
- Evaluation of FeCl3 efficacy in a mouse wound infection model.
Main Results:
- FeCl3 at 200 µM killed >99.9% of P. aeruginosa cells.
- FeCl3-induced cell death showed hallmarks of ferroptosis (ROS burst, lipid peroxidation, DNA damage).
- FeCl3-hydrogel treatment cleared wound pus and promoted healing in mice.
Conclusions:
- FeCl3 induces microbial ferroptosis in P. aeruginosa.
- FeCl3 demonstrates high therapeutic potential for P. aeruginosa wound infections.
- Iron compounds offer a promising alternative to antibiotics.
