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Chitosan and current challenges in the fight against antibiotic resistence

The importance of antibiotics remains undiminished today. However, antibiotic resistance is increasing and few new agents are being discovered that can bypass them. In the following article, a chitosan-based nanomaterial was therefore developed that exploits the antimicrobial effect of chitosan to eliminate Salmonella typhimurium.

ELIMINATION OF INTRACELLULAR SALMONELLA TYPHIMURIUM WITH ACID-TRANSFORMING CHITOSAN AND FRAGMENT DNA POLYPLEXES

Eradication of Intracellular Salmonella Typhimurium by Polyplexes of Acid-Transforming Chitosan and Fragment DNA. Julius A. Edson, Weiping Chu, Steffen Porwollik, Kaycee Tran, Nathalie Iribe, Michael McClelland, and Young Jik Kwon. Macromolecular Bioscience, Volume 21, Issue 7, 2000408, https://doi.org/10.1002/mabi.202000408

Currently, existing strategies for identifying and using antimicrobial substances from microorganisms are reaching their limits. A new strategy to combat antibiotic resistance is the use of materials with unique biophysical properties such as chitosan. With developments in nanotechnology, nanoantibiotics could be produced from these materials. Chitosan exhibits antimicrobial activity against a broad spectrum of gram positive and gram negative bacteria. However, its application has so far been limited by its low solubility in water at pH values above 6.
Intracellular pathogenic microbes such as Salmonella Typhimurium multiply inside host cells.  Thus, they bypass the humoral immune system of the host organism. The Gram-negative S. Typhimurium bacteria infect humans and other mammals by altering the cytoskeleton of host cells and invading slightly acidic endosomes (pH about 5).
In this study, chitosan was modified at the oxygen of the C6 atom with diglycolamine to form an acetal. The acid-transforming chitosan (ATC) produced exhibits greatly improved water solubility. In an acidic environment, the acetal group is hydrolyzed to form chitosan again, where it can exert its antimicrobial activity. To improve uptake into target cells, nanoparticles were formed from cationic ATC and anionic fragment DNA (fDNA).
These nanoparticles are stable at the physiological pH of 7.4, but are rapidly degraded in the acidic environment of lysosomes, thereby releasing ATC.

RESULTS

The efficacy of ATC/fDNA nanospheres was evaluated using S. Typhimurium and RAW264.7 macrophages. At pH values of 5.5 and 7.4, less than 50% of S. Typhimurium bacteria survived. The effect of ATC/fDNA polyplexes was best at high doses at pH 5.5. Compared to chitosan, the ATC/fDNA nanoparticles showed antimicrobial activity even at pH 7.4. Chitosan and the nanoparticles did not exhibit acute toxicity to macrophages.

Conclusion: The investigated ATC/fDNA nanoparticles were able to eliminate intracellular S. Typhimurium bacteria without being toxic to host cells. The high stability and solubility at the physiological pH of 7.4 may allow systematic administration. But further experiments are needed regarding possible chronic toxicity and usability of the nanoantibiotic in vitro. Link to article: https://onlinelibrary.wiley.com/doi/10.1002/mabi.202000408

chitosan, nanoparticles, antibacterial, antibiotics

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