Ferric chloride induces ferroptosis in Pseudomonas aeruginosa and heals wound infection in a mouse model

Huang, Minmin1; Wang, Zhen1; Yao, Lishan1; Zhang, Lei2; Gou, Xingchun3,4; Mo, Haizhen1; Li, Hongbo1; Hu, Liangbin1; Zhou, Xiaohui5

2023-05-01

10.1016/j.ijantimicag.2023.106794

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS   Impact Factor & Quartile

0924-8579

1872-7913

Background: Pseudomonas aeruginosa is one of the most common pathogens that lead to fatal human in-fection. This Gram-negative pathogen has evolved complex drug resistance, which poses significant chal-lenges 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 mu M 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, in-cluding reactive oxygen species (ROS) burst, lipid peroxidation, and DNA damage. Catalase or Fe2 + chela-tor alleviated FeCl3-mediated cell death, indicating that H2O2 and labile Fe2 + induced the Fenton reac-tion 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 treat-ment, 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.(c) 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

Pseudomonas aeruginosa FeCl 3 ferroptosis hydrogels polyvinyl alcohol-boric acid hydrogels

SCI

English

Corresponding

National Natural Science Foundation of China["32172321","31901795"] ; Shenzhen Science and Technology Innovation Commission[JCYJ20220818100616034] ; Innovation Capability Support Program of Shaanxi Province[2023-CX-TD-61]

Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy

Infectious Diseases ; Microbiology ; Pharmacology & Pharmacy

WOS:000983796000001

ELSEVIER

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Shaanxi Univ Sci & Technol, Sch Food Sci & Engn, Xian 710021, Peoples R China
2.Univ Alberta, Edmonton, AB, Canada
3.Xian Med Univ, Shaanxi Key Lab Brain Disorders, Xian 710021, Peoples R China
4.Xian Med Univ, Inst Basic & Translat Med, Xian 710021, Peoples R China
5.Southern Univ Sci & Technol, Sch Publ Hlth & Emergency Management, Shenzhen, Guangdong, Peoples R China

Huang, Minmin,Wang, Zhen,Yao, Lishan,et al. Ferric chloride induces ferroptosis in Pseudomonas aeruginosa and heals wound infection in a mouse model[J]. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS,2023,61(5).

Huang, Minmin.,Wang, Zhen.,Yao, Lishan.,Zhang, Lei.,Gou, Xingchun.,...&Zhou, Xiaohui.(2023).Ferric chloride induces ferroptosis in Pseudomonas aeruginosa and heals wound infection in a mouse model.INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS,61(5).

Huang, Minmin,et al."Ferric chloride induces ferroptosis in Pseudomonas aeruginosa and heals wound infection in a mouse model".INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS 61.5(2023).