4.5 Article

Concentration Ranges of Antibacterial Cations for Showing the Highest Antibacterial Efficacy but the Least Cytotoxicity against Mammalian Cells: Implications for a New Antibacterial Mechanism

期刊

CHEMICAL RESEARCH IN TOXICOLOGY
卷 28, 期 9, 页码 1815-1822

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acs.chemrestox.5b00258

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资金

  1. National Basic Research Program of China [2012CB619100]
  2. National Natural Science Foundation of China [51372087, 81271957, 51232002, 51072057]
  3. National Institutes of Health [EB015190]
  4. National Science Foundation [CMMI-1234957]
  5. Department of Defense Congressionally Directed Medical Research Program, Oklahoma Center for Adult Stem Cell Research [434003]
  6. Oklahoma Center for the Advancement of Science and Technology [HR14-160]

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Antibacterial metal ions, such as Ag+, Zn2+ and Cu2+, have been extensively used in medical implants and devices due to their strong broad spectrum of antibacterial activity. However, it is still a controversial issue as to whether they can show the desired antibacterial activity while being toxic to mammalian cells. It is very important to balance their antibacterial effectiveness with minimal damage to mammalian cells. Toward this end, this study is to identify the suitable concentrations of these three ions at which they can effectively kill two types of clinically relevant bacteria (Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli)) but show no obvious cytotoxicity on fibroblasts. Such concentration ranges are found to be 2.5 x 10(-7) M-10(-6) M, 10(-5) M-10(-4) M, and 10(-5) M-10(-4) M for Ag+, Zn2+, and Cu2+, respectively. Investigation of their antibacterial mechanism shows that these three metal ions all show antibacterial property through a mechanism of damaging bacterial cell membranes by the generation of reactive oxygen species but surprisingly preserving the integrity of bacterial genomic DNA. The encouraging results indicate that antibacterial metal ions with controlled concentrations can bring considerable benefits to biomedical applications.

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