UV-Based Advanced Oxidation Processes and Nanoscale Antimicrobials for Antibiotic Resistance Mitigation
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Abstract
Antibiotic resistance (AR) is an ongoing pandemic that is unnoticed by many. AR is a global public health issue that challenges therapeutic potential against pathogens of humans and animals. Predictably, the environment has been implicated in the widespread AR in clinical settings. Wastewater treatment plants (WWTPs) are considered major sources for the release of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) into the environment. In this regard, effective wastewater treatment can serve as a barrier to the release of AR determinants into the environment. Also, addressing AR threats involves eliminating the development of new resistant traits by developing alternative antimicrobials with novel non-specific low-mutation bacterial targets.This study presented advanced oxidation processes (AOPs) that utilize the strong oxidizing power of hydroxyl radical ({HO}^.) and sulphate radical (S{O_4}^{.-}) as promising technologies for ARGs degradation. Also, we evaluated antimicrobial nanoparticles (NPs) that inactivate microorganisms via non-specific actions as alternatives to conventional antibiotics against pathogens of clinical concerns. The reaction kinetics study, in Chapter 2, investigated the degradation of intracellular (i-) and extracellular (e-) plasmid-encoded tetA, ampR and sul1 ARGs using UV254, {HO}^. and SO_4^{.-}\ UV-based AOP (UV254/H2O2 and UV254/S2O82-, respectively). The degradation of tetA, ampR and sul1 was quantified using quantitative polymerase chain reaction (qPCR). Damages to each ARG were observed using two qPCR amplicons ranging between 162-1054 bp. Culture-based horizontal gene transformation experiments were used to estimate the deactivation kinetics of pCR™2.1-TOPO AR plasmid. The results from this study provide data useful for setting operating conditions in WWTPs, drinking water treatments, and reactor designs for effective ARGs removal. In Chapter 3, we investigated the antibacterial synergy of photosensitizer (PS) -AgNP conjugates using protoporphyrin IX (PpIX) as PS. The study examined the oxidation of AgNPs for an accelerated release of Ag+ and the influence of positive surface coating of polyethyleneimine (PEI) in promoting NPs-bacterial interactions. The antimicrobial activities of three NPs: AgNPs and cysPpIX-AgNPs, PEI-cysPpIX-AgNPs against a methicillin-resistant Staphylococcus aureus (MRSA) strain and a wild-type multidrug-resistant (MDR) E. coli were reported. This study outlined the crucial role of optimized Ag+ release for enhanced performance of AgNP-based antimicrobials. Furthermore, Chapter 4 evaluated the use of nanoscale monocaprin as the first line of defense agent against the entrance of intracellular pathogens like E. coli and SARS-CoV-2. The sonochemistry technique was applied for the synthesis of nano-monocaprin to improve the solubility and antimicrobial activity of monocaprin. The study compared the inactivation of phi6 and E. coli using nano-monocaprin and bulk-monocaprin by plaque assay and drop plate colony count method, respectively. This study showed that nano-monocaprin formulations have improved antimicrobial properties relative to monocaprin at the molecular scale.