Abstract
The resistance of bacteria towards traditional antibiotics currently constitutes one of the most important health care issues with serious negative impacts in practice. Overcoming this issue can be achieved by using antibacterial agents with multimode antibacterial action. Silver nano-particles (AgNPs) are one of the well-known antibacterial substances showing such multimode antibacterial action. Therefore, AgNPs are suitable candidates for use in combinations with traditional antibiotics in order to improve their antibacterial action. In this work, a systematic study quantifying the synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was performed. Employing the microdilution method as more suitable and reliable than the disc diffusion method, strong synergistic effects were shown for all tested antibiotics combined with AgNPs at very low concentrations of both antibiotics and AgNPs. No trends were observed for synergistic effects of antibiotics with different modes of action and different chemical structures in combination with AgNPs, indicating non-specific synergistic effects. Moreover, a very low amount of silver is needed for effective antibacterial action of the antibiotics, which represents an important finding for potential medical applications due to the negligible cytotoxic effect of AgNPs towards human cells at these concentration levels.
Highlights
IntroductionSilver nanoparticles (AgNPs) were shown to inactivate bacterial enzymes [8,9], disrupt bacterial metabolic processes [10,11,12] and the bacterial cell wall, accumulate in the cytoplasmic membrane, increase its permeability [9,13,14], collapse the plasma membrane potential [12], interact with DNA [8], and generate reactive oxygen species [15,16,17], which damage biomacromolecules [18]
An ever-increasing resistance of bacteria to the effects of existing antimicrobial agents is currently one of the most important health care issues with serious negative impacts such as higher morbidityMolecules 2016, 21, 26; doi:10.3390/molecules21010026 www.mdpi.com/journal/moleculesMolecules 2016, 21, 26 and mortality rates in patients with infections caused by multi-resistant bacteria [1,2]
AgNPs of an average size of 28 nm with a narrow size distribution were synthesized by the modified Tollens process and stabilized by gelatin to achieve high antibacterial efficiency by preventing particle aggregation in culture media
Summary
Silver nanoparticles (AgNPs) were shown to inactivate bacterial enzymes [8,9], disrupt bacterial metabolic processes [10,11,12] and the bacterial cell wall, accumulate in the cytoplasmic membrane, increase its permeability [9,13,14], collapse the plasma membrane potential [12], interact with DNA [8], and generate reactive oxygen species [15,16,17], which damage biomacromolecules [18] Thanks to their multi-level mode of action, AgNPs destroy or inhibit the growth of pathogenic microorganisms, including highly resistant bacterial strains (from units to several tens of mg/L) [13,14,19,20,21,22].
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