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Silver enhances antibiotic activity against gram-negative bacteria
J Ruben Morones-Ramirez1,2, Jonathan A Winkler1,3, Catherine S Spina4,2
1Howard Hughes Medical Institute, Department of Biomedical Engineering and Center of Synthetic Biology, Boston University, Boston, MA 02215, USA.
Science Translational Medicine
|June 21, 2013
Summary
Silver enhances antibiotic effectiveness against difficult Gram-negative bacteria by disrupting cellular processes and increasing oxidative stress. This approach restores antibiotic susceptibility and combats resistant strains, biofilms, and persister cells.
Area of Science:
- Antimicrobial research
- Bacterial physiology
- Drug discovery
Background:
- Declining antibiotic pipeline necessitates novel antimicrobial strategies.
- Gram-negative pathogens pose significant treatment challenges.
- Silver's antimicrobial properties are known, but its mechanism is unclear.
Purpose of the Study:
- Investigate silver's mechanism of action against bacteria.
- Determine if silver can potentiate existing antibiotic therapies.
- Explore silver's efficacy in combination with antibiotics against resistant strains, biofilms, and persister cells.
Main Methods:
- In vitro assays assessing bacterial growth and susceptibility.
- In vivo studies using mouse models of urinary tract infection and peritonitis.
- Analysis of silver's impact on bacterial cellular processes, including oxidative stress and membrane permeability.
Main Results:
- Silver disrupts bacterial metabolism, iron homeostasis, and disulfide bond formation.
- Silver increases reactive oxygen species production and membrane permeability in Gram-negative bacteria.
- Silver potentiates a range of antibiotics against Gram-negative bacteria, restores susceptibility in resistant strains, sensitizes bacteria to vancomycin, and enhances eradication of persister cells and biofilms.
Conclusions:
- Silver can be effectively combined with existing antibiotics to combat Gram-negative bacterial infections.
- Silver's ability to induce oxidative stress and disrupt cellular processes strengthens the antimicrobial arsenal.
- This strategy offers a promising approach to overcome antibiotic resistance and treat challenging infections.
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