King Saud University
Permanent URI for this collectionhttps://drepo.sdl.edu.sa/handle/20.500.14154/4095
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Item Restricted Testing Combinations of Engineered Nanomaterials and Conventional Antimicrobial Agents Against Clinical Isolates Antimicrobial Resistant Bacteria from Saudi Arabia Hospital(Saudi Digital Library, 2023-01-31) Alotaibi, Areej Monawar; Alsaleh, NasserAntimicrobial-resistant (AMR) bacteria have emerged as a global threat to healthcare systems, coinciding with antimicrobial agent development shortages over the past few years. Several inorganic engineered nanomaterials (ENMs), precisely synthesized materials within a size range of 1–100 nanometers (nm), show promising biomedical applications, including antimicrobial properties. Notably, silver (AgNPs) and zinc oxide (ZnONPs) nanoparticles have demonstrated superior antimicrobial properties against AMR bacteria, mediated through multiple antimicrobial mechanisms simultaneously. However, one major challenge for using ENMs is their toxicity. Therefore, studies in this thesis aimed to investigate the antimicrobial activities of several ENM-based combinations with conventional antimicrobial agents against wild-type and clinical isolates AMR bacteria. Specifically, we sought to determine the minimal inhibitory concentrations (MIC) values of commercial (cm-AgNPs; 54nm), locally synthesized (co-AgNPs; 79nm), ZnONPs (400nm), and six conventional antimicrobial agents. After that, we determined the potential synergy between nanoparticles and these antimicrobial agents against wild-type Gram- positive and Gram-negative bacteria as well as AMR-Klebsiella pneumoniae strains clinically isolated from King Khaled University Hospital, King Saud University, Riyadh. Lastly, our studies also included the assessment of cytotoxicity of ENM-based synergistic combinations in an in vitro human hepatocyte model. The results showed that cm-AgNPs had excellent antibacterial activity against Gram-negative bacteria, with MICs ranging from 16 to 128 μg/mL; however, it had minimal antimicrobial activity against Gram- positive bacteria (MICs= 256 μg/mL). The co-AgNPs displayed minimal antibacterial responses against Gram-positive and Gram-negative bacteria, which might be attributed to their high agglomeration in bacterial media (Cation-adjusted Mueller-Hinton broth). Moreover, ZnONPs exhibited no antibacterial activity against Escherichia coli (E.coli) or Staphylococcus aureus at the tested concentrations (up to 192 μg/mL). Therefore, only cm- AgNPs was used in subsequent studies. Treatment with cm-AgNPs resulted in excellent synergy with antimicrobial agents, including kanamycin, colistin, rifampicin, and vancomycin, against wild-type E.coli and three AMR-K.pneumoniae strains, while combinations of cm-AgNPs and ampicillin or ciprofloxacin displayed no synergy. We speculate that such synergy might be due to AgNPs-induced cell membrane interaction, thereby facilitating antimicrobial agent entry into bacteria. Importantly, these synergistic combinations demonstrated minimal to no toxicity in the liver cells. Together, studies reported in this thesis demonstrate the potential therapeutic use of cm-AgNPs against AMR bacteria.69 0