Novel copper-containing ferrite nanoparticles exert lethality to MRSA by disrupting MRSA cell membrane permeability, depleting intracellular iron ions, and upregulating ROS levels
ObjectiveThe widespread use of antibiotics has inevitably led to the emergence of multidrug-resistant bacterial strains, such as methicillin-resistant Staphylococcus aureus (MRSA), making treatment of this infection a serious challenge. This study aimed to explore new treatment strategies for MRSA i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1023036/full |
| _version_ | 1811168215654465536 |
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| author | Jinhua Ye Fangpeng Hou Fangpeng Hou Guanyu Chen Tianyu Zhong Junxia Xue Fangyou Yu Yi Lai Yingjie Yang Dedong Liu Yuantong Tian Junyun Huang |
| author_facet | Jinhua Ye Fangpeng Hou Fangpeng Hou Guanyu Chen Tianyu Zhong Junxia Xue Fangyou Yu Yi Lai Yingjie Yang Dedong Liu Yuantong Tian Junyun Huang |
| author_sort | Jinhua Ye |
| collection | DOAJ |
| description | ObjectiveThe widespread use of antibiotics has inevitably led to the emergence of multidrug-resistant bacterial strains, such as methicillin-resistant Staphylococcus aureus (MRSA), making treatment of this infection a serious challenge. This study aimed to explore new treatment strategies for MRSA infection.MethodsThe structure of Fe3O4 NPs with limited antibacterial activity was optimized, and the Fe2+ ↔ Fe3+ electronic coupling was eliminated by replacing 1/2 Fe2+ with Cu2+. A new type of copper-containing ferrite nanoparticles (hereinafter referred to as Cu@Fe NPs) that fully retained oxidation–reduction activity was synthesized. First, the ultrastructure of Cu@Fe NPs was examined. Then, antibacterial activity was determined by testing the minimum inhibitory concentration (MIC) and safety for use as an antibiotic agent. Next, the mechanisms underlying the antibacterial effects of Cu@Fe NPs were investigated. Finally, mice models of systemic and localized MRSA infections was established for in vivo validation.ResultsIt was found that Cu@Fe NPs exhibited excellent antibacterial activity against MRSA with MIC of 1 μg/mL. It effectively inhibited the development of MRSA resistance and disrupted the bacterial biofilms. More importantly, the cell membranes of MRSA exposed to Cu@Fe NPs underwent significant rupture and leakage of the cell contents. Cu@Fe NPs also significantly reduced the iron ions required for bacterial growth and contributed to excessive intracellular accumulation of exogenous reactive oxygen species (ROS). Therefore, these findings may important for its antibacterial effect. Furthermore, Cu@Fe NPs treatment led to a significant reduction in colony forming units within intra-abdominal organs, such as the liver, spleen, kidney, and lung, in mice with systemic MRSA infection, but not for damaged skin in those with localized MRSA infection.ConclusionThe synthesized nanoparticles has an excellent drug safety profile, confers high resistant to MRSA, and can effectively inhibit the progression of drug resistance. It also has the potential to exert anti-MRSA infection effects systemically in vivo. In addition, our study revealed a unique multifaceted antibacterial mode of Cu@Fe NPs: (1) an increase in cell membrane permeability, (2) depletion of Fe ions in cells, (3) generation of ROS in cells. Overall, Cu@Fe NPs may be potential therapeutic agents for MRSA infections. |
| first_indexed | 2024-04-10T16:23:31Z |
| format | Article |
| id | doaj.art-61f133462e9a4981831300daca1a8156 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-10T16:23:31Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-61f133462e9a4981831300daca1a81562023-02-09T10:18:27ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-02-011410.3389/fmicb.2023.10230361023036Novel copper-containing ferrite nanoparticles exert lethality to MRSA by disrupting MRSA cell membrane permeability, depleting intracellular iron ions, and upregulating ROS levelsJinhua Ye0Fangpeng Hou1Fangpeng Hou2Guanyu Chen3Tianyu Zhong4Junxia Xue5Fangyou Yu6Yi Lai7Yingjie Yang8Dedong Liu9Yuantong Tian10Junyun Huang11Analytical Laboratory of Basic Medical College, Gannan Medical University, Ganzhou, Jiangxi, ChinaCenter for Immunology, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, ChinaDepartment of Chemistry and Biochemistry, Kent State University, Kent, OH, United StatesDepartment of Clinical Laboratory, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, ChinaCenter for Immunology, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi, ChinaDepartment of Clinical Laboratory, Shanghai Pulmonary Hospital of Tongji University, Shanghai, ChinaCenter for Immunology, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi, ChinaCenter for Immunology, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, Jiangxi, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, ChinaPharmacology Department, Gannan Medical University, Ganzhou, Jiangxi, ChinaDepartment of Clinical Laboratory, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, ChinaObjectiveThe widespread use of antibiotics has inevitably led to the emergence of multidrug-resistant bacterial strains, such as methicillin-resistant Staphylococcus aureus (MRSA), making treatment of this infection a serious challenge. This study aimed to explore new treatment strategies for MRSA infection.MethodsThe structure of Fe3O4 NPs with limited antibacterial activity was optimized, and the Fe2+ ↔ Fe3+ electronic coupling was eliminated by replacing 1/2 Fe2+ with Cu2+. A new type of copper-containing ferrite nanoparticles (hereinafter referred to as Cu@Fe NPs) that fully retained oxidation–reduction activity was synthesized. First, the ultrastructure of Cu@Fe NPs was examined. Then, antibacterial activity was determined by testing the minimum inhibitory concentration (MIC) and safety for use as an antibiotic agent. Next, the mechanisms underlying the antibacterial effects of Cu@Fe NPs were investigated. Finally, mice models of systemic and localized MRSA infections was established for in vivo validation.ResultsIt was found that Cu@Fe NPs exhibited excellent antibacterial activity against MRSA with MIC of 1 μg/mL. It effectively inhibited the development of MRSA resistance and disrupted the bacterial biofilms. More importantly, the cell membranes of MRSA exposed to Cu@Fe NPs underwent significant rupture and leakage of the cell contents. Cu@Fe NPs also significantly reduced the iron ions required for bacterial growth and contributed to excessive intracellular accumulation of exogenous reactive oxygen species (ROS). Therefore, these findings may important for its antibacterial effect. Furthermore, Cu@Fe NPs treatment led to a significant reduction in colony forming units within intra-abdominal organs, such as the liver, spleen, kidney, and lung, in mice with systemic MRSA infection, but not for damaged skin in those with localized MRSA infection.ConclusionThe synthesized nanoparticles has an excellent drug safety profile, confers high resistant to MRSA, and can effectively inhibit the progression of drug resistance. It also has the potential to exert anti-MRSA infection effects systemically in vivo. In addition, our study revealed a unique multifaceted antibacterial mode of Cu@Fe NPs: (1) an increase in cell membrane permeability, (2) depletion of Fe ions in cells, (3) generation of ROS in cells. Overall, Cu@Fe NPs may be potential therapeutic agents for MRSA infections.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1023036/fullMRSACu@Fe NPsantibacterial mechanismcell membraneFeROS |
| spellingShingle | Jinhua Ye Fangpeng Hou Fangpeng Hou Guanyu Chen Tianyu Zhong Junxia Xue Fangyou Yu Yi Lai Yingjie Yang Dedong Liu Yuantong Tian Junyun Huang Novel copper-containing ferrite nanoparticles exert lethality to MRSA by disrupting MRSA cell membrane permeability, depleting intracellular iron ions, and upregulating ROS levels Frontiers in Microbiology MRSA Cu@Fe NPs antibacterial mechanism cell membrane Fe ROS |
| title | Novel copper-containing ferrite nanoparticles exert lethality to MRSA by disrupting MRSA cell membrane permeability, depleting intracellular iron ions, and upregulating ROS levels |
| title_full | Novel copper-containing ferrite nanoparticles exert lethality to MRSA by disrupting MRSA cell membrane permeability, depleting intracellular iron ions, and upregulating ROS levels |
| title_fullStr | Novel copper-containing ferrite nanoparticles exert lethality to MRSA by disrupting MRSA cell membrane permeability, depleting intracellular iron ions, and upregulating ROS levels |
| title_full_unstemmed | Novel copper-containing ferrite nanoparticles exert lethality to MRSA by disrupting MRSA cell membrane permeability, depleting intracellular iron ions, and upregulating ROS levels |
| title_short | Novel copper-containing ferrite nanoparticles exert lethality to MRSA by disrupting MRSA cell membrane permeability, depleting intracellular iron ions, and upregulating ROS levels |
| title_sort | novel copper containing ferrite nanoparticles exert lethality to mrsa by disrupting mrsa cell membrane permeability depleting intracellular iron ions and upregulating ros levels |
| topic | MRSA Cu@Fe NPs antibacterial mechanism cell membrane Fe ROS |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1023036/full |
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