Antibiotic-Loaded Gold Nanoparticles: A Nano-Arsenal against ESBL Producer-Resistant Pathogens

Abstract

The advent of new antibiotics has helped clinicians to control severe bacterial infections. Despite this, inappropriate and redundant use of antibiotics, inadequate diagnosis, and smart resistant mechanisms developed by pathogens sometimes lead to the failure of treatment strategies. The genotypic analysis of clinical samples revealed that the rapid spread of extended-spectrum β-lactamases (ESBLs) genes is one of the most common approaches acquired by bacterial pathogens to become resistant. The scenario compelled the researchers to prioritize the design and development of novel and effective therapeutic options. Nanotechnology has emerged as a plausible groundbreaking tool against resistant infectious pathogens. Numerous reports suggested that inorganic nanomaterials, specifically gold nanoparticles (AuNPs), have converted unresponsive antibiotics into potent ones against multi-drug resistant pathogenic strains. Interestingly, after almost two decades of exhaustive preclinical evaluations, AuNPs are gradually progressively moving ahead toward clinical evaluations. However, the mechanistic aspects of the antibacterial action of AuNPs remain an unsolved puzzle for the scientific fraternity. Thus, the review covers state-of-the-art investigations pertaining to the efficacy of AuNPs as a tool to overcome ESBLs acquired resistance, their applicability and toxicity perspectives, and the revelation of the most appropriate proposed mechanism of action. Conclusively, the trend suggested that antibiotic-loaded AuNPs could be developed into a promising interventional strategy to limit and overcome the concerns of antibiotic-resistance.

Keywords: ESBLs; antibiotic resistance; bacterial pathogens; gold nanoparticles; nano-therapeutics.

Figure 1

Advantages of AuNPs as a carrier of antibiotics.

Figure 2

Various approaches used for the synthesis of antibiotic-loaded AuNPs. (a) Two or multi-step approach, (b) a single-step approach.

Figure 3

Schematic description of revival of β-lactam antibiotics by AuNPs. (a) Bacterial pathogens develop resistance towards β-lactam antibiotics; (b) AuNPs were synthesized using the same ineffective β-lactam antibiotic as reducing and stabilizing agent; (c) β-lactam antibiotic after loading to AuNPs become potent against the same β-lactam resistant bacterial pathogen.

Figure 4

Comparison between (a) bacterial resistance mechanism and (b) plausible mechanism of action of AuNPs to overcome resistance. (a1) Modification of porins to hinder the entry of antibiotics, whereas (b1) same antibiotics, once loaded to AuNPs, gain easy entry into the bacterial pathogen; (a2) efflux of antibiotics from bacteria to outside of the cell, whereas (b2) inhibition of efflux pumps/decreasing expression of efflux pump genes by AuNPs; (a3) alteration of antibiotic target site, whereas, (b3) indirect/direct targeting of bacterial biomolecules by AuNPs; (a4) Antibiotic inactivating enzymes (ESBLs), whereas (b4) saturation of enzymes or direct damage to the enzyme structure by AuNPs. In addition, (b5) AuNPs can directly interact with the cell barriers, causing perforation and cell lysis.