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The use of novel silver-lignin nanoparticles against multidrug-resistant bacteria

University of British Columbia

The continuous emergence of multidrug-resistant (MDR) bacteria is one of the bigger problems that threatens our world today. The increased level of MDR strains has resulted in not only rendering many antibiotics useless, but has also generated an urgent need for new antimicrobial treatment. One promising antimicrobial therapy being investigated is the use of nanoparticles. In this study, silver-lignin nanoparticles (AgLNPs) were formed using silver and lignin as a reducing and capping agent. These particles were made using green synthesis, meaning no environmentally harmful reagents were used to enhance efficacy, yet were still able to retain antibacterial activity. AgLNPs were characterized using microscopic and spectrophotometric methodologies. Formed AgLNPs were approximately 20 nm in size with a 0.15 ± 0.2 polydispersity index and -34.2 mV ζ-potential. The antimicrobial activity was tested using a broth microdilution assay and particles were able to inhibit MDR clinical isolates including common pathogens Staphyloccocus aureus and Pseudomonas aeruginosa, amongst others, at 5-10 µg/mL, up to 5 times more effectively than their AgNP counterparts. MTT assays showed that AgLNPs were toxic to THP-1 and A549 cell lines at 25 µg/mL, and toxic to fibroblast cells at 1 µg/mL. The particles also induced the release of cytokine IL-10 in THP-1 cells, which promotes an anti-inflammatory response. Lastly, transcriptomic analysis using RNA-seq and RT-qPCR was performed using P. aeruginosa to elucidate resistance mechanisms. Genes responsible for efflux function and internal quorum sensing genes were upregulated; however, non-efflux gene functions were downregulated suggesting AgLNP internalization. Cytotoxicity was exhibited by the AgLNPs towards human cells, with a significantly high toxicity in fibroblast cells. Still, they remain of interest as their many functional groups facilitate modifications, meaning these could be worked with in the future, and altered to potentially decrease cytotoxicity. Additionally, the AgLNPs used in these study could have external uses, such as surface coatings.

Text

2022-01-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/76978

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/