Mechanistic Study of the Synergistic Antibacterial Activity of Combined Silver Nanoparticles and Common Antibiotics

Abstract

A combination of silver nanoparticles (AgNPs) and an antibiotic can synergistically inhibit bacterial growth, especially against the drug-resistant bacteria Salmonella typhimurium. However, the mechanism for the synergistic activity is not known. This study chooses four classes of antibiotics, β-lactam (ampicillin and penicillin), quinolone (enoxacin), aminoglycoside (kanamycin and neomycin), and polykeptide (tetracycline) to explore their synergistic mechanism when combined with AgNPs against the multidrug-resistant bacterium Salmonella typhimurium DT 104. Enoxacin, kanamycin, neomycin, and tetracycline show synergistic growth inhibition against the Salmonella bacteria when combined with AgNPs, while ampicillin and penicillin do not. UV–vis and Raman spectroscopy studies reveal that all these four synergistic antibiotics can form complexes with AgNPs, while ampicillin and penicillin do not. The presence of tetracycline enhances the binding of Ag to Salmonella by 21% and Ag+ release by 26% in comparison to that without tetracycline, while the presence of penicillin does not enhance the binding of Ag or Ag+ release. This means that AgNPs first form a complex with tetracycline. The tetracycline–AgNPs complex interacts more strongly with the Salmonella cells and causes more Ag+ release, thus creating a temporal high concentration of Ag+ near the bacteria cell wall that leads to growth inhibition of the bacteria. These findings agree with the recent findings that Ag+ release from AgNPs is the agent causing toxicity.

Synergism in the Antibacterial Action of Ternary Mixtures Involving Silver Nanoparticles, Chitosan and Antibiotics

“…The mechanisms proposed involve the formation of chemical bonds among the antibiotic molecules and the AgNP surfaces, which work as a drug delivery systems. [31][32][33][34][35][36]49,50 Such propositions are in agreement with the assumption here presented, since the three used drugs have antibacterial activities involving intracellular interference in the metabolism of DNA or RNA. Their uptakes take place due to the affinity of silver surfaces for the bacterial membranes, probably followed by the release of the antibiotic molecules in the intracellular medium due to the oxidation of the AgNP surfaces.…”

Vancomycin-modified Fe₃O₄@SiO₂@Ag microflowers as effective antimicrobial agents

“…Studies showed that the antimicrobial properties of Ag materials rely on free Ag ions, which can not only bind to sulfur, oxygen, and nitrogen of essential enzymes, resulting in bacterial cell death, but also react with DNA to prevent unwinding, resulting in serious damage to bacterial cells. 29,50,51 Moreover, the Ag NPs itself can directly deactivate the sulfur-containing proteins of cell membrane, causing functional damage to the membrane and the structural changes. 52 On the other hand, vancomycin is a potent antibiotic against Gram-positive bacteria and exerts antibacterial activity by forming hydrogen bonds with the peptidoglycan terminus D-Ala-D-Ala on the cell wall.…”

“…[27][28][29][30] For example, Brown et al indicated the effective synergistic effect of noble metal NPs functionalized with ampicillin against multiresistant strains. 31 Lai et al reported a general route for preparing vancomycin-modified Au NPs; the products act as effective broad-spectrum bactericides against both Gram-negative and Gram-positive pathogens.…”

Novel Synthesis and Characterization of Doxycycline‐Loaded Gold Nanoparticles: The Golden Doxycycline for Antibacterial Applications

“…Deng et al have shown the synergic effect of amoxicillin with silver nanoparticles against Escherichia coli . Rai et al used cefaclor as both reducing and capping agent to produce spherical gold nanoparticles and showed a potent activity against both Gram‐positive and Gram‐negative bacteria .…”

“…In this paper, we combined AuNPs with DOXY by three chemical different methodologies (DOXY‐AuNPs, DOXY‐ON‐AuNPs, DOXY IN‐AuNPs) and, evaluated the antimicrobial effect of these hybrids on several bacterial species in the presence of AuNPs synthesized. Therefore, the development of a simple and fast method to improve the activity of DOXY and oxytetracycline has become increasingly attractive …”