Mechanisms of antibiotic resistance in bacteria mediated by silver nanoparticles

Abstract

Silver nanoparticles (AgNPs) are widely used in industry, consumer products, and medical appliances due to their efficient antimicrobial properties. However, information on environmental toxicity and bacterial impact of these particles is not completely elucidated. Results showed that AgNPs produced growth inhibition and oxidative stress in bacteria Escherichia coli (gram negative) and Staphylococcus aureus (gram positive), with half-maximal inhibitory concentrations (IC) of 12 and 7 mg/L, respectively. Surprisingly, bacteria pre-exposed to sublethal dose of AgNPs exhibited increased resistance toward antibiotics (ampicillin and Pen-Strep) with IC elevated by 3-13-fold. Further, AgNP pre-exposure raised the minimal inhibitory concentration and minimal biocidal concentration by two- to eightfold when cells were challenged with antibiotics with diverse mechanisms of action (penicillin, chloramphenicol, and kanamycin). Interestingly, we found that upon exposure to ampicillin, strains pretreated with AgNPs exhibited lower levels of membrane damage and oxidative stress, together with elevated levels of intracellular ATP relative to untreated cells. Bacterial reverse mutation assay (Ames test) showed that AgNPs are highly mutagenic, consistent with further assays demonstrating abiotic reactive oxygen species (ROS) generation and intrinsic DNA cleavage activity in vitro of AgNPs. Overall, our results suggest that AgNPs enhance bacterial resistance to antibiotics by promoting stress tolerance through induction of intracellular ROS. Our data suggest potential consequences of incidental environmental exposure of bacteria to AgNPs and indicate the need to regulate use and disposal of AgNPs in industry and consumer products.

Potential antibacterial mechanism of silver nanoparticles and the optimization of orthopedic implants by advanced modification technologies

“…In a recent report, it was found that AgNPs enhanced bacterial resistance to antibiotics by promoting stress tolerance through induction of intracellular ROS. 51 In addition, Gram-negative bacteria Escherichia coli 013, Pseudomonas aeruginosa CCM 3955, and E. coli CCM 3954 can develop resistance to AgNPs after repeated exposure. This resistance was due to the production of flagellin, an adhesive protein of the bacterial flagellum, which caused the aggregation of AgNPs and thereby eliminated their antibacterial effect.…”

Antimicrobial Nanoparticles: applications and mechanisms of action

“…39 Kaweeteerawat, et al showed that prolonged exposure of E. coli and S. aureus to AgNPs led to development of resistance to AgNP due to the selective proliferation of surviving resistant cells. 40 AgNP treatment was also suggested to cause physiological changes in bacteria leading to antibiotic resistance. 40 Furthermore, aluminium nanoparticles have been shown to promote conjugative transfer of plasmids, including those with antibiotic resistance genes, resulting in dissemination of these genes within the species as well as to other species of the genus.…”

“…40 AgNP treatment was also suggested to cause physiological changes in bacteria leading to antibiotic resistance. 40 Furthermore, aluminium nanoparticles have been shown to promote conjugative transfer of plasmids, including those with antibiotic resistance genes, resulting in dissemination of these genes within the species as well as to other species of the genus.…”

Detection of Genes Related to Resistance to Silver Nanoparticles in Bacteria from Secondary Endodontic Infections

“…For example, Kaweeteerawat et al exposed gramnegative (E. coli) and gram-positive bacteria (S. aureus) at sublethal doses of silver nanoparticles and observed an increase in the minimum inhibitory concentrations after only four rounds of subculturing. The authors of this article did not investigate the participation of silver ion efflux pumps from the RND family in this type of resistance [32]. Mishra et al treated Enterobacter cloacae 13047 and multidrug resistance Enterobacter cloacae, with a sublethal concentration of AgNPs (6 mg/ml) and silver-metal-carbohydrate nanoparticle (Ag-MCNPs) (0.75 mg/ml) for 0, 30, 60, 120, and 180 min.…”