Ferrous sulfate-loaded hydrogel cures Staphylococcus aureus infection via facilitating a ferroptosis-like bacterial cell death in a mouse keratitis model

Wang，Zhen1; Li，Hongbo1; Zhou，Wei2; Lee，Jintae3; Liu，Zhenbin1; An，Zhixing4; Xu，Dan1; Mo，Haizhen1; Hu，Liangbin1; Zhou，Xiaohui5

2022-11-01

10.1016/j.biomaterials.2022.121842

BIOMATERIALS   Impact Factor & Quartile

0142-9612

1878-5905

Hydrogels loaded with ampicillin, vancomycin or other antibiotics are one of the most widely used therapeutic agents for keratitis caused by Staphylococcus aureus. However, emergence of methicillin-resistant S. aureus (MRSA) makes infections harder to be treated by antibiotic-based hydrogels, urging the development of novel antibacterial materials. Inspired by mammalian ferroptosis, we determined the bactericidal effects of ferrous sulfate (FeSO) on S. aureus, and evaluated the therapeutic potential of FeSO-loaded hydrogel in a mouse keratitis model. The results showed that FeSO facilitated ferroptosis-like cell death in S. aureus with the key characteristics of reactive oxygen species (ROS) generation and lipid peroxidation. Notably, FeSO also efficiently killed persisters and MRSA, and eliminated biofilms of S. aureus. RNA profiles demonstrated that ferroptosis-related genes were significantly up-regulated, and the genes responsible for cell wall and cell membrane biosynthesis were down-regulated after exposure to Fe, supporting the occurrence of ferroptosis and cell lysis. We further prepared a FeSO-loaded hydrogel by using hyaluronic acid (HA) and ascorbate. The FeSO hydrogel has the characteristics of injectability, self-healing, uniform distribution of Fe in the three-dimensional gel structure, appropriate fluidity, high-water retention, high efficacy to kill MRSA, and excellent biocompatibility. In a mouse keratitis model, we showed that treatment of animals with FeSO hydrogel led to a rapid recovery of from keratitis, prevented the dissimilation of MRSA to the lung, and alleviated systemic inflammation, demonstrating the therapeutic potential of FeSO hydrogel. Taken together, our results indicated that FeSO hydrogel is a promising alternative to current antibiotics-dependent therapeutic materials for the treatment of infections by MRSA.

Ferroptosis Ferrous sulfate FeSO4-Loaded hydrogel Keratitis MRSA Staphylococcus aureus

SCI

English

Corresponding

National Key Research and Development Program of China[2019YFC1606302];National Natural Science Foundation of China[31901795];National Natural Science Foundation of China[32172321];

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:000867565000003

ELSEVIER SCI LTD

MATERIALS SCIENCE

2-s2.0-85139291784

Scopus

1.School of Food and Biological Engineering,Shaanxi University of Science and Technology,Xi'an,China
2.School of Food Science,Henan Institute of Science and Technology,Xinxiang,China
3.School of Chemical Engineering,Yeungnam University,Gyeongsan,280 Daehak-Ro, Gyeongbuk,South Korea
4.College of Animal Science and Veterinary Medicine,Henan Institute of Science and Technology,Xinxiang,China
5.School of Public Health and Emergency Management,Southern University of Science and Technology,ShenZhen,Guangdong,China

Wang，Zhen,Li，Hongbo,Zhou，Wei,et al. Ferrous sulfate-loaded hydrogel cures Staphylococcus aureus infection via facilitating a ferroptosis-like bacterial cell death in a mouse keratitis model[J]. BIOMATERIALS,2022,290.

Wang，Zhen.,Li，Hongbo.,Zhou，Wei.,Lee，Jintae.,Liu，Zhenbin.,...&Zhou，Xiaohui.(2022).Ferrous sulfate-loaded hydrogel cures Staphylococcus aureus infection via facilitating a ferroptosis-like bacterial cell death in a mouse keratitis model.BIOMATERIALS,290.

Wang，Zhen,et al."Ferrous sulfate-loaded hydrogel cures Staphylococcus aureus infection via facilitating a ferroptosis-like bacterial cell death in a mouse keratitis model".BIOMATERIALS 290(2022).