Antibiotics | Silver Nanoparticle-Antibiotic Combinations Overcome Multidrug-Resistant Bacteria

This study systematically evaluated the antibacterial effects of biosynthesized silver nanoparticles (Bio-AgNPs) combined with antibiotics such as ampicillin and enrofloxacin, revealing their potential in overcoming multidrug-resistant bacteria. Experimental validation demonstrated that this combination significantly enhances antibiotic sensitivity, reduces resistance development, and improves membrane permeability.

 

Literature Overview
This article, 'Silver Nanoparticle–Antibiotic Combinations: A Strategy to Overcome Bacterial Resistance in Escherichia coli, Salmonella Enteritidis and Staphylococcus aureus', published in the 'Antibiotics' journal, reviews and summarizes the role of silver nanoparticles combined with antibiotics in antimicrobial therapy, particularly their application in controlling drug-resistant bacterial infections. The study emphasizes the global challenge of antibiotic resistance and proposes silver nanoparticles as an effective adjuvant therapy, potentially enhancing antimicrobial effects by altering cell membrane permeability and facilitating antibiotic entry into bacterial cells.

Background Knowledge
Antibiotic resistance has become a major global public health issue, particularly in clinical and veterinary medicine, where the spread of resistant strains significantly increases treatment difficulties and infection-related mortality. Silver nanoparticles (AgNPs), due to their unique antimicrobial mechanisms and high surface area-to-volume ratios, have been extensively studied as alternative agents against drug-resistant bacteria. However, certain bacteria may develop resistance to AgNPs through genomic variations, limiting their use as standalone treatments. Studies indicate that combining AgNPs with antibiotics may produce synergistic or additive effects, enhancing antimicrobial activity and reducing resistance selection. This combinatorial approach offers new possibilities for treating multidrug-resistant (MDR) bacteria while decreasing dose-dependent toxicity of individual agents, laying the foundation for future development.

 

 

Research Methods and Experiments
The study evaluated the antimicrobial activity of Bio-AgNPs, ampicillin (AMP), and enrofloxacin (ENRO) used alone or in combination against Escherichia coli, Salmonella Enteritidis, and Staphylococcus aureus. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined using the broth microdilution method. Checkerboard assays were employed to analyze interactions between antimicrobial agents, while time-kill curves assessed the bactericidal kinetics of combination therapy. Additionally, mechanisms such as FTIR, membrane permeability, ROS generation, and efflux pump inhibition were analyzed.

Key Conclusions and Perspectives

• All bacterial strains exhibited increased MIC values after prolonged antibiotic exposure, confirming resistance development. Only E. coli developed resistance to Bio-AgNPs; however, the Bio-AgNP + AMP combination restored sensitivity to E. coli.
• FTIR analysis indicated no chemical bonding between Bio-AgNPs and antibiotics, suggesting independent antimicrobial mechanisms. The combination effects likely resulted from biological interactions. Membrane permeability experiments showed that Bio-AgNPs and combination treatments increased membrane permeability, facilitating antibiotic entry into bacterial cells.
• ROS detection demonstrated that Bio-AgNPs alone or in combination could reduce ROS levels, indicating potential antioxidant properties related to the plant extracts used in their synthesis. Additionally, the combination therapy did not significantly inhibit efflux pumps, suggesting that the antimicrobial mechanism may be associated with changes in membrane permeability.
• The study found that S. Enteritidis and S. aureus did not develop cross-resistance following combination therapy, indicating advantages of silver nanoparticles in preventing resistance selection.

Research Significance and Prospects
This study highlights the potential of Bio-AgNP combined with AMP or ENRO in combating MDR bacteria, providing a basis for developing safer and less toxic antimicrobial treatment strategies. Future studies should further evaluate the cytotoxicity, oxidative stress response, and in vivo efficacy of these combinations to validate their clinical and veterinary applications.

 

 

Conclusion
This study systematically evaluated the application of silver nanoparticles (Bio-AgNPs) combined with conventional antibiotics in antimicrobial therapy, revealing that the combinations significantly enhance antimicrobial activity by altering bacterial membrane permeability and facilitating antibiotic entry into cells. Although some strains developed resistance to Bio-AgNPs, the combination therapy effectively restored antibiotic sensitivity and prevented cross-resistance in most cases. The study also suggests that silver nanoparticles may possess antioxidant properties, potentially reducing damage to host tissues. These effects may be linked to the plant extracts used during nanoparticle synthesis. Future research should further assess in vivo antimicrobial efficacy and safety to advance clinical application of this strategy.

 

Mariana Homem de Mello Santos, Thiago Hideo Endo, Sara Scandorieiro, Renata Katsuko Takayama Kobayashi, and Gerson Nakazato. Silver Nanoparticle–Antibiotic Combinations: A Strategy to Overcome Bacterial Resistance in Escherichia coli, Salmonella Enteritidis and Staphylococcus aureus. Antibiotics.