| Summary |
Globally rising antibiotic-resistant (AR) and multi-drug resistant (MDR) bacterial infections are of public health concern due to lower efficacy of current antibiotic therapy. Specifically, Hospital Acquired Infections (HAIs) or nosocomial Infections pose a significant threat to public health, with an alarming rise in cases attributed to pathogens like Escherichia coli and Pseudomonas aeruginosa. These infections not only lead to increased morbidity and mortality rates but also impose substantial economic burdens on healthcare systems worldwide. Given the persistent challenge of antibiotic resistance, there is an urgent need for innovative and sustainable solutions to curb the prevalence of HAIs. E. coli causes surgical wound infections, bloodstream infections, sepsis, and urinary tract infections, among others. P. aeruginosa causes cystic fibrosis, meningitis, septicemia, endophthalmitis. This study explores the application of novel amino-functionalized silver nanoparticles (NH₂-AgNP) and nanotechnology as a promising strategy to combat the proliferation of E. coli and P. aeruginosa in healthcare settings, thereby reducing the burden of HAIs and antibiotic resistance. Utilizing the unique physicochemical properties of NH₂-AgNP, including their high surface-to-volume ratio and inherent antimicrobial activity, this research investigates their efficacy in inhibiting the growth and spread of these multidrug-resistant pathogens. Herein, we tested the antibacterial efficacy, mode of action (MoA), and safety of novel amino-functionalized silver nanoparticles (NH₂-AgNP) against two AR E. coli strains (i.e., ampicillin-resistant, and kanamycin-resistant E. coli), including a susceptible strain of E. coli DH5[alpha] and P. aeruginosa. Complementary toxicity bioassays were performed, and results were confirmed using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Our results showed that ampicillin and kanamycin did not inhibit growth in both AR E. coli strains with doses up to 160 [mu]g/mL tested, and up to 20 [mu]g/mL for P. aeruginosa. Treatment with [greater-than-or-equal-to]1 [mu]g/mL NH₂-AgNP significantly inhibited the growth of all three E. coli strains, and at [greater-than-or-equal-to]10 [mu]g/mL inhibited the growth of P. aeruginosa, suggesting a broad-spectrum bactericidal activity of NH₂-AgNP. The DLS analyses showed significant cell leakage and cell debris formation over time with NH₂-AgNP treatment for all bacterial strains tested and this was confirmed by TEM. Further combined treatment of NH₂-AgNP with ampicillin or kanamycin showed antagonistic effects, suggesting that combination treatment is less effective than NH₂-AgNP alone treatment. Based on these findings, we propose two MoA for NH₂-AgNP: (i) electrostatic interactions, followed by (ii) cell wall damage. Furthermore, in vitro safety assessment revealed that NH₂-AgNP was noncytotoxic and antioxidative to primary human lung epithelial cells. These findings suggest that NH₂-AgNP may serve as an effective and safer bactericidal therapy as an alternative to current antibiotics and could help combat rising HAI associated with AR/MDRO, thereby protecting global public health. This dissertation advances the field of public health by proposing an alternative antibacterial agent to address global public health challenges. The implications of this research for public health protection are multifaceted. Firstly, the successful integration of NH₂-AgNP in hospital environments could significantly reduce the incidence of HAIs, thereby enhancing patient safety and healthcare outcomes. Secondly, the development of targeted nanotechnology-based antibacterial agent, NH₂-AgNP, may support combating antibiotic-resistant pathogens, providing a sustainable alternative to conventional antimicrobial agents. Thirdly, this research contributes to the growing body of knowledge on the applications of nanomedicine in the field of healthcare, paving the way for the development of novel and effective strategies for infectious disease control. Overall, this study underscores the critical role of interdisciplinary research in addressing the global challenge of HAIs and emphasizes the potential of nanotechnology as a transformative tool for promoting public health and mitigating the impact of pathogenic bacterial diseases in the healthcare setting. Further clinical studies are needed to determine the efficacy and safety of NH₂-AgNP in patients with nosocomial infections, and other possible medical applications of NH₂-AgNP could be explored such as its use in diagnostics and medical device and implant coating. |
