Enhancement of antibiotics antimicrobial activity due to the silver nanoparticles impact on the cell membrane

PLoS One. 2019 Nov 8;14(11):e0224904. doi: 10.1371/journal.pone.0224904. eCollection 2019.

Abstract

The ability of microorganisms to generate resistance outcompetes with the generation of new and efficient antibiotics; therefore, it is critical to develop novel antibiotic agents and treatments to control bacterial infections. An alternative to this worldwide problem is the use of nanomaterials with antimicrobial properties. Silver nanoparticles (AgNPs) have been extensively studied due to their antimicrobial effect in different organisms. In this work, the synergistic antimicrobial effect of AgNPs and conventional antibiotics was assessed in Gram-positive and Gram-negative bacteria. AgNPs minimal inhibitory concentration was 10-12 μg mL-1 in all bacterial strains tested, regardless of their different susceptibility against antibiotics. Interestingly, a synergistic antimicrobial effect was observed when combining AgNPs and kanamycin according to the fractional inhibitory concentration index, FICI: <0.5), an additive effect by combining AgNPs and chloramphenicol (FICI: 0.5 to 1), whereas no effect was found with AgNPs and β-lactam antibiotics combinations. Flow cytometry and TEM analysis showed that sublethal concentrations of AgNPs (6-7 μg mL-1) altered the bacterial membrane potential and caused ultrastructural damage, increasing the cell membrane permeability. No chemical interactions between AgNPs and antibiotics were detected. We propose an experimental supported mechanism of action by which combinatorial effect of antimicrobials drives synergy depending on their specific target, facilitated by membrane alterations generated by AgNPs. Our results provide a deeper understanding about the synergistic mechanism of AgNPs and antibiotics, aiming to combat antimicrobial infections efficiently, especially those by multi-drug resistant microorganisms, in order to mitigate the current crisis due to antibiotic resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Infective Agents / pharmacology
  • Cell Membrane / drug effects*
  • Cell Membrane / ultrastructure
  • Cell Membrane Permeability
  • Drug Resistance, Microbial
  • Membrane Potentials / drug effects
  • Metal Nanoparticles* / chemistry
  • Metal Nanoparticles* / ultrastructure
  • Microbial Sensitivity Tests
  • Silver* / chemistry

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Silver

Grants and funding

This work was supported by AHS: DGAPA-UNAM [Grant No. IN210618] and CONACyT [Grant No. 284385]; KOJM: CONACyT [Grant No. 269071]; and NB: Bionanotechnology International Network. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.