2. Academic Validation
  3. Ferrous gluconate triggers ferroptosis in Escherichia coli: Implications of lipid peroxidation and DNA damage

Ferrous gluconate triggers ferroptosis in Escherichia coli: Implications of lipid peroxidation and DNA damage

  • Microbiol Res. 2024 Jul:284:127711. doi: 10.1016/j.micres.2024.127711.
Wenhui Jing 1,  Rongxian Guo 2,  Xiaolin Zhu 1,  Shurui Peng 1,  Hongbo Li 1,  Dan Xu 1,  Liangbin Hu 3,  Haizhen Mo 4
Affiliations

Affiliations

  • 1 School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China.
  • 2 Laboratory of Functional Microbiology and Animal Health, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471003, China; Luoyang Key Laboratory of Live Carrier Biomaterial and Animal Disease Prevention and Control, Luoyang 471003, China.
  • 3 School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China. Electronic address: hulb@sust.edu.cn.
  • 4 School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China. Electronic address: mohz@sust.edu.cn.
PMID: 38636240 DOI: 10.1016/j.micres.2024.127711
Abstract

Microbial Ferroptosis has been proved to combat drug-resistant pathogens, but whether this pattern can be applied to the prevention and control of Escherichia coli remains to be further explored. In this study, ferrous gluconate (FeGlu) showed remarkable efficacy in killing E. coli MG1655 with a mortality rate exceeding 99.9%, as well as enterotoxigenic E. coli H10407 (ETEC H10407) and enterohemorrhagic E. coli O157:H7 (EHEC O157:H7). Bacteria death was instigated by the infiltration of Fe2+, accompanied by a burst of intracellular Reactive Oxygen Species (ROS) and lipid peroxidation. Notably, mitigating lipid peroxidation failed to alleviate death of E. coli. Further findings confirmed that FeGlu induced DNA damage, and ΔrecA mutant showed more sensitive, implicating that DNA damage was involved in the death of E. coli. The direct interaction of Fe2+ with DNA was demonstrated by fluorescent staining, gel electrophoresis, and circular dichroism (CD). Moreover, proteomic analysis unveiled 50 differentially expressed proteins (DEPs), including 18 significantly down-regulated proteins and 32 significantly up-regulated proteins. Among them, the down-regulation of SOS-responsive transcriptional suppressor LexA indicated DNA damage induced severely by FeGlu. Furthermore, FeGlu influenced pathways such as fatty acid metabolism (FadB, FadE), iron-sulfur cluster assembly (IscA, IscU, YadR), iron binding, and DNA-binding transcription, along with α-linolenic acid metabolism, fatty acid degradation, and pyruvate metabolism. These pathways were related to FeGlu stress, including lipid peroxidation and DNA damage. In summary, FeGlu facilitated Ferroptosis in E. coli through mechanisms involving lipid peroxidation and DNA damage, which presents a new strategy for the development of innovative antimicrobial strategies targeting E. coli infections.

Keywords

Escherichia coli; Ferroptosis; Ferrous gluconate; Proteomic analysis; SOS response.

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