Evolutionary Adaptation of Priority Pathogen Acinetobacter baumannii to Nanoparticulate and Ionic Forms of Silver
- Publication Type:
- Thesis
- Issue Date:
- 2023
Open Access
Copyright Clearance Process
- Recently Added
- In Progress
- Open Access
This item is open access.
The escalating threat of antimicrobial resistance (AMR) necessitates immediate, innovative solutions to combat it. Silver nanoparticles (nanosilver; NAg) have emerged as one of the most commercialised alternative antimicrobial agents, renowned for their multi-targeting and broad-spectrum antimicrobial properties. Worringly, the widespread and often indiscriminate use of these nanoparticles has raised concerns over the emergence of silver-resistant bacteria. This thesis herein describes, for the first time, the ability of Acinetobacter baumannii, an important Gram-negative coccobacillus bacterium, and an ESKAPE pathogen (the group of six leading hospital-acquired bacterial pathogens), to evolve stable resistance to NAg. The model ATCC 19606 strain was able to proliferate at otherwise toxic nanoparticle concentrations following prolonged exposure. Remarkably, the bacterium also demonstrated a distinct adaptation trait to the ionic form of silver (Ag+), exhibiting a ‘slower-to-kill’ tolerance phenotype, a silver defence phenomenon also not previously seen in A. baumannii. Comparative whole genome analysis detected stable silver-induced gene mutations in the NAg-resistant (NAgR) and Ag+-tolerant (Ag+T) strains. Detailed molecular studies revealed shifts in gene expression patterns in the silver-adapted strains in response to varied concentrations of the respective silver antimicrobials. The study identified tiered primary and secondary defence mechanisms that enable the bacteria to protect itself against the key cell envelope targeting and oxidative stress-mediated toxicity mechanisms of the silver agents. Notably, there were clear overlaps in defence responses between the silver-adapted bacteria to both NAg and Ag+, despite their distinct adaptation characteristics. This thesis ultimately provides insights into the molecular basis of nanoparticulate and ionic silver defence in A. baumannii ATCC 19606, shedding light on how the bacterium physiologically evolved because of continual silver exposure. The elucidation of the adaptation phenomena can help enable future drug design that can target bacterial defence mechanisms to overcome evolutionary adaptation. The findings of this work caution against the indiscriminate use of antimicrobial silver and stress the need for implementing effective regulatory strategies to manage the responsible application silver-based products to ensure their continued and long-term use in the future.
Please use this identifier to cite or link to this item: