Bacterial vaginosis (BV) is the most common vaginal infection found in women in the world. Due to increasing drug-resistance of virulent pathogen such asGardnerella vaginalis(G. vaginalis), more than half of BV patients suffer recurrence after antibotics treatment. Here, metastable iron sulfides (mFeS) act in a Gram-dependent manner to kill bacteria, with the ability to counteract resistantG. vaginalisfor BV treatment. With screening of iron sulfide minerals, metastable Fe3S4shows suppressive effect on bacterial growth with an order: Gram-variableG. vaginalis>Gram-negative bacteria>> Gram-positive bacteria. Further studies on mechanism of action (MoA) discover that the polysulfide species released from Fe3S4selectively permeate bacteria with thin wall and subsequently interrupt energy metabolism by inhibiting glucokinase in glycolysis, and is further synergized by simultaneously released ferrous iron that induces bactericidal damage. Such multiple MoAs enable Fe3S4to counteractG. vaginalisstrains with metronidazole-resistance and persisters in biofilm or intracellular vacuole, without developing new drug resistance and killing probiotic bacteria. The Fe3S4regimens successfully ameliorate BV with resistantG. vaginalisin mouse models and eliminate pathogens from patients suffering BV. Collectively, mFeS represent an antibacterial alternative with distinct MoA able to treat challenged BV and improve women health.
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Metastable Iron Sulfides Gram-Dependently Counteract ResistantGardnerella Vaginalisfor Bacterial Vaginosis Treatment,Adv Sci, 5 Feb 2022
Advanced Science, 5 February, 2022, DOI：https://doi.org/10.1002/advs.202104341
Metastable Iron Sulfides Gram-Dependently Counteract ResistantGardnerella Vaginalisfor Bacterial Vaginosis Treatment
Ling Fang, Ruonan Ma, Xuejiao J. Gao, Lei Chen, Yuan Liu, Yanwu Huo, Taotao Wei, Xiaonan Wang, Qian Wang, Haojue Wang, Chengjun Cui, Qifeng Shi, Jing Jiang, Lizeng Gao
Abstract
Bacterial vaginosis (BV) is the most common vaginal infection found in women in the world. Due to increasing drug-resistance of virulent pathogen such asGardnerella vaginalis(G. vaginalis), more than half of BV patients suffer recurrence after antibotics treatment. Here, metastable iron sulfides (mFeS) act in a Gram-dependent manner to kill bacteria, with the ability to counteract resistantG. vaginalisfor BV treatment. With screening of iron sulfide minerals, metastable Fe3S4shows suppressive effect on bacterial growth with an order: Gram-variableG. vaginalis>Gram-negative bacteria>> Gram-positive bacteria. Further studies on mechanism of action (MoA) discover that the polysulfide species released from Fe3S4selectively permeate bacteria with thin wall and subsequently interrupt energy metabolism by inhibiting glucokinase in glycolysis, and is further synergized by simultaneously released ferrous iron that induces bactericidal damage. Such multiple MoAs enable Fe3S4to counteractG. vaginalisstrains with metronidazole-resistance and persisters in biofilm or intracellular vacuole, without developing new drug resistance and killing probiotic bacteria. The Fe3S4regimens successfully ameliorate BV with resistantG. vaginalisin mouse models and eliminate pathogens from patients suffering BV. Collectively, mFeS represent an antibacterial alternative with distinct MoA able to treat challenged BV and improve women health.
文章链接：https://onlinelibrary.wiley.com/doi/10.1002/advs.202104341
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