Tannic Acid-Stabilized Silver Nanoparticles Used in Biomedical Application as an Effective Antimelioidosis and Prolonged Efflux Pump Inhibitor against Melioidosis Causative Pathogen

Molecules. 2021 Feb 14;26(4):1004. doi: 10.3390/molecules26041004.

Abstract

Burkholderia pseudomallei is the causative pathogen of melioidosis and this bacterium is resistant to several antibiotics. Silver nanoparticles (AgNPs) are an interesting agent to develop to solve this bacterial resistance. Here, we characterize and assess the antimelioidosis activity of AgNPs against these pathogenic bacteria. AgNPs were characterized and displayed a maximum absorption band at 420 nm with a spherical shape, being well-monodispersed and having high stability in solution. The average size of AgNPs is 7.99 ± 1.46 nm. The antibacterial efficacy of AgNPs was evaluated by broth microdilution. The bactericidal effect of AgNPs was further assessed by time-kill kinetics assay. Moreover, the effect of AgNPs on the inhibition of the established biofilm was investigated by the crystal violet method. In parallel, a study of the resistance induction development of B. pseudomallei towards AgNPs with efflux pump inhibiting effect was performed. We first found that AgNPs had strong antibacterial activity against both susceptible and ceftazidime-resistant (CAZ-resistant) strains, as well as being efficiently active against B. pseudomallei CAZ-resistant strains with a fast-killing mode via a bactericidal effect within 30 min. These AgNPs did not only kill planktonic bacteria in broth conditions, but also in established biofilm. Our findings first documented that the resistance development was not induced in B. pseudomallei toward AgNPs in the 30th passage. We found that AgNPs still showed an effective efflux pump inhibiting effect against these bacteria after prolonged exposure to AgNPs at sublethal concentrations. Thus, AgNPs have valuable properties for being a potent antimicrobial agent to solve the antibiotic resistance problem in pathogens.

Keywords: biofilm inhibition; biomedical application; efflux pump inhibition; mechanism; melioidosis; resistance induction; silver nanoparticles.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Burkholderia pseudomallei / drug effects
  • Burkholderia pseudomallei / physiology*
  • Ceftazidime / pharmacology
  • Ceftazidime / therapeutic use
  • Drug Resistance, Bacterial / drug effects
  • Dynamic Light Scattering
  • Kinetics
  • Melioidosis / drug therapy*
  • Melioidosis / microbiology*
  • Metal Nanoparticles / therapeutic use*
  • Metal Nanoparticles / ultrastructure
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Phenotype
  • Silver / pharmacology
  • Silver / therapeutic use*
  • Static Electricity
  • Tannins / pharmacology
  • Tannins / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Tannins
  • Silver
  • Ceftazidime