Development of Novel Peptide-Modified Silver Nanoparticle-Based Rapid Biosensors for Detecting Aminoglycoside Antibiotics

The extensive use of antibiotics leading to the rapid spread of antibiotic resistance poses high health risks to humans, but to date there is still lack of a quantitative model to properly assess the risks. Concerns over the health risk of antibiotic residues in the environment are mainly (1) the potential hazard of ingested antibiotic residues in the environment altering the human microbiome and promoting emergence and selection for bacteria resistance inhabiting the human body, and (2) the potential hazard of creating a selection pressure on environmental microbiome and leading to reservoirs of antibiotic resistance in the environment. We provide a holistic view of health risk assessment of antibiotic resistance associated with antibiotic residues in the environment in contrast with that of the antibiotic resistant bacteria and discuss the main knowledge gaps and the future research that should be prioritized to achieve the quantitative risk assessment. We examined and summarized the available data and information on the four core elements of antibiotic resistance associated with antibiotic residues in the environment: hazard identification, exposure assessment, dose-response assessment, and risk characterization. The data required to characterize the risks of antibiotic residues in the environment is severely limited. The main future research needs have been identified to enable better assessments of antibiotic resistance associated with antibiotic residues in the environment: (1) establishment of a standardized monitoring guide of antibiotic residues and antibiotic resistance in the environment, (2) derivation of the relationship between antibiotic levels and pathogenic antibiotic-resistance development in different settings, and (3) establishment of the dose-response relationship between pathogenic antibiotic resistant bacteria and various infection diseases. After identification of key risk determinant parameters, we propose a conceptual framework of human health risk assessments of antibiotic residues in the environment. CAPSULE: A holistic view of human health risk assessment of antibiotic residues in the environment was provided.

The impact of capping agents and environmental conditions (pH, ionic strength, and background electrolytes) on surface charge and aggregation potential of silver nanoparticles (AgNPs) suspensions were investigated. Capping agents are chemicals used in the synthesis of nanoparticles to prevent aggregation. The AgNPs examined in the study were as follows: (a) uncoated AgNPs (H(2)-AgNPs), (b) electrostatically stabilized (citrate and NaBH(4)-AgNPs), (c) sterically stabilized (polyvinylpyrrolidone (PVP)-AgNPs), and (d) electrosterically stabilized (branched polyethyleneimine (BPEI)-AgNPs)). The uncoated (H(2)-AgNPs), the citrate, and NaBH(4)-coated AgNPs aggregated at higher ionic strengths (100 mM NaNO(3)) and/or acidic pH (3.0). For these three nanomaterials, chloride (Cl(-), 10 mM), as a background electrolyte, resulted in a minimal change in the hydrodynamic diameter even at low pH (3.0). This was limited by the presence of residual silver ions, which resulted in the formation of stable negatively charged AgCl colloids. Furthermore, the presence of Ca(2+) (10 mM) resulted in aggregation of the three previously identified AgNPs regardless of the pH. As for PVP coated AgNPs, the ionic strength, pH and electrolyte type had no impact on the aggregation of the sterically stabilized AgNPs. The surface charge and aggregation of the BPEI coated AgNPs varied according to the solution pH.

Aminoglycoside antibiotics are used as prophylaxis, or urgent treatment, for many life-threatening bacterial infections, including tuberculosis, sepsis, respiratory infections in cystic fibrosis, complex urinary tract infections and endocarditis. Although aminoglycosides are clinically-essential antibiotics, the mechanisms underlying their selective toxicity to the kidney and inner ear continue to be unraveled despite more than 70 years of investigation. The following mechanisms each contribute to aminoglycoside-induced toxicity after systemic administration: (1) drug trafficking across endothelial and epithelial barrier layers; (2) sensory cell uptake of these drugs; and (3) disruption of intracellular physiological pathways. Specific factors can increase the risk of drug-induced toxicity, including sustained exposure to higher levels of ambient sound, and selected therapeutic agents such as loop diuretics and glycopeptides. Serious bacterial infections (requiring life-saving aminoglycoside treatment) induce systemic inflammatory responses that also potentiate the degree of ototoxicity and permanent hearing loss. We discuss prospective clinical strategies to protect auditory and vestibular function from aminoglycoside ototoxicity, including reduced cochlear or sensory cell uptake of aminoglycosides, and otoprotection by ameliorating intracellular cytotoxicity.