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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. [ABSTRACT FROM AUTHOR]

Candida albicans is the most leading cause of life-threatening fungal invasive infections, especially for vulvovaginal candidiasis (VVC). Resistance and tolerance to common fungicide has risen great demands on alternative strategies for treating C. albicans infections. In the present study, ferroptosis has been proven to occur in C. albicans by directly exposed to FeSO 4 via induing hallmarks of ferroptosis, including Fe2+ overload burden, ROS eruption and lipid peroxidation. Transcriptomic profile gave the great hints of the possible mechanism for fungal ferroptosis that FeSO 4 disturb pathways associated to ribosome, tyrosine metabolism, triglyceride metabolism and thiamine metabolism, thus mobilizing death-related gene synthesis. Inspired by the results, a FeSO 4 -loaded hydrogel was prepared as an antifungal agent to treat C. albicans infection. This hydrogel exhibited excellent dressing properties and maintained superior antifungal activity by characterization tests. Besides, mice treated by this composite hydrogel displayed excellent therapeutic efficacy. These results highlighted the potential therapeutic use of FeSO 4 as an innovative strategy in treating C. albicans infections by targeting ferroptosis. [Display omitted] • Prove the occurrence of ferroptosis in C. albicans for the first time. • Highlight the potential therapeutic use of Fe2+ in treating C. albicans infections. • New insights for the mechanism of ferroptosis in fungi. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes frequently causes Listeriosis in humans and animals. In present study, we discovered that in the presence of FeSO 4 , L. monocytogenes became viable but non-culturable (VBNC), and remained virulent to Caenorhabditis elegans. The killing assay indicated that these VBNC cells kept sensitive to tetracycline, differing from dormant cells. Transcriptomic analysis revealed more gene transcription occurrence in the VBNC cells compared to dormant cells, involving stress response and ribosome binding. No ferroptosis hallmarks were observed in the VBNC cells, whereas the application of either intracellular Fe2+ chelator or the ferroptosis inhibitor arrested the formation of VBNC state by FeSO 4 , as well as by Benzakonium chloride or Haz-Tab. This implicated the universal involvement of intracellular Fe2+ and other cascades related to ferroptosis in the formation of VBNC state in L. monocytogenes. Taken together, we discovered an iron-induced VBNC state in L. monocytogenes , and provided clues to further understanding their potential risks. [ABSTRACT FROM AUTHOR]