Evaluation of cold atmospheric pressure plasma effects on Pseudomonas aeruginosa wound infection in a mouse model
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Abstract
Background and Objectives: Antibiotic resistance in microorganisms is a significant global health concern. Cold atmospheric plasma is an innovative and promising method for inactivating bacteria. This study aimed to evaluate the effects of cold plasma on Pseudomonas aeruginosa in a mouse wound infection model.
Materials and Methods: The disk diffusion method was used to perform antibiograms after isolating the bacteria. A multidrug-resistant strain was then selected. The bactericidal activity of cold helium plasma was investigated in vitro. The optimal cold plasma conditions were determined in the laboratory, with a flow of 3 liters per minute and a power of 1.1 watts. These conditions were later used for in vivo evaluations.
Results: In a laboratory study, helium gas plasma treatment for 8 minutes reduced P. aeruginosa by 2.5 logs. In the in vivo study, plasma reduced the wound's microbial load in mice by 1.9 log. The antibiotic treatment group had a 1.2 log reduction. Both plasma and antibiotic therapies had similar effects on microbial inactivation.
Conclusion: The overall evaluation of wound healing time and pathological features showed that plasma was generally better than antibiotic treatment. Plasma can inactivate P. aeruginosa in wounds and accelerate wound healing.
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16. Mendes-Oliveira G, Jensen JL, Keener KM, Campanella OH. Modeling the inactivation of Bacillus subtilis spores during cold plasma sterilization. Innov Food Sci Emerg Technol 2019; 52: 334-342.
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18. Isbary G, Heinlin J, Shimizu T, Zimmermann JL, Morfill G, Schmidt HU, et al. Successful and safe use of 2 min cold atmospheric argon plasma in chronic wounds: Results of a randomized controlled trial. Br J Dermatol 2012; 167: 404-410.
19. Langner I, Kramer A, Matthes R, Rebert F, Kohler C, Koban I, et al. Inhibition of microbial growth by cold atmospheric plasma compared with the antiseptics chlorhexidine digluconate, octenidine dihydrochloride, and polyhexanide. Plasma Process Polym 2019; 16: 1800162.
20. Turner KH, Everett J, Trivedi U, Rumbaugh KP, Whiteley M. Requirements for Pseudomonas aeruginosa acute burn and chronic surgical wound infection. PLoS Genet 2014; 10(7): e1004518.
21. Xiong Z (2018). Cold Atmospheric Pressure Plasmas (CAPs) for Skin Wound Healing. In: Plasma Medicine - Concepts and Clinical Applications. https://www.intechopen.com/chapters/60721
22. Ermolaeva SA, Varfolomeev AF, Chernukha MY, Yurov DS, Vasiliev MM, Kaminskaya AA, et al. Bactericidal effects of non-thermal argon plasma in vitro, in biofilms and in the animal model of infected wounds. J Med Microbiol 2011; 60: 75-83.
23. Xu G-M, Shi X-M, Cai J-F, Chen S-L, Li P, Yao C-W, et al. Dual effects of atmospheric pressure plasma jet on skin wound healing of mice. Wound Repair Regen 2015; 23: 878-884.
24. Chatraie M, Torkaman G, Khani M, Salehi H, Shokri B. In vivo study of non-invasive effects of non-thermal plasma in pressure ulcer treatment. Sci Rep 2018; 8: 5621.
25. Kubinova S, Zaviskova K, Uherkova L, Zablotskii V, Churpita O, Lunov O, et al. Non-thermal air plasma promotes the healing of acute skin wounds in rats. Sci Rep 2017; 7: 45183.
26. Boekema BKHL, Hofmann S, Van Ham BJT, Bruggeman PJ, Middelkoop E. Antibacterial plasma at safe levels for skin cells. J Phys D Appl Phys 2013; 46: 422001.
27 Boekema BKHL, Vlig M, Guijt D, Hijnen K, Hofmann S, Smits P, et al. A new flexible DBD device for treating infected wounds: In vitro and ex vivo evaluation and comparison with a RF argon plasma jet. J Phys D Appl Phys 2016; 49: 044001.
2. Arndt S, Unger P, Wacker E, Shimizu T, Heinlin J, Li Y-F, et al. Cold atmospheric plasma (CAP) changes gene expression of key molecules of the wound healing machinery and improves wound healing in vitro and in vivo. PLoS One 2013; 8(11): e79325.
3. Rijal BP, Satyal D, Parajuli NP. High burden of antimicrobial resistance among bacteria causing pyogenic wound infections at a tertiary care hospital in Kathmandu, Nepal. J Pathog 2017; 2017: 9458218.
4. Ferro TAF, Souza EB, Suarez MAM, Rodrigues JFS, Pereira DMS, Mendes SJF, et al. Topical application of cinnamaldehyde promotes faster healing of skin wounds infected with Pseudomonas aeruginosa. Molecules 2019; 24: 1627.
5. Engler AC, Wiradharma N, Ong ZY, Coady DJ, Hedrick JL, Yang YY. Emerging trends in macromolecular antimicrobials to fight multi-drug-resistant infections. Nano Today 2012; 7: 201-222.
6. Bourke P, Ziuzina D, Han L, Cullen PJ, Gilmore BF. Microbiological interactions with cold plasma. J Appl Microbiol 2017; 123: 308-324.
7. Hoffmann C, Berganza C, Zhang J. Cold Atmospheric Plasma: Methods of production and application in dentistry and oncology. Med Gas Res 2013; 3: 21.
8. Kong MG, Kroesen G, Morfill G, Nosenko T, Shimizu T, Van Dijk J, et al. Plasma medicine: An introductory review. New J Phys 2009; 11: 115012.
9. Han L, Patil S, Boehm D, Milosavljević V, Cullen PJ, Bourke P. Mechanisms of inactivation by high-voltage atmospheric cold plasma differ for Escherichia coli and Staphylococcus aureus. Appl Environ Microbiol 2015; 82: 450-458.
10. Fridman G, Brooks AD, Balasubramanian M, Fridman A, Gutsol A, Vasilets VN, et al. Comparison of direct and indirect effects of non-thermal atmospheric-pressure plasma on bacteria. Plasma Process Polym 2007; 4: 370-375.
11. Mohd Nasir N, Lee BK, Yap SS, Thong KL, Yap SL. Cold plasma inactivation of chronic wound bacteria. Arch Biochem Biophys 2016; 605: 76-85.
12. Ercan UK, Smith J, Ji H-F, Brooks AD, Joshi SG. Chemical changes in nonthermal Plasma-Treated N-Acetylcysteine (NAC) solution and their contribution to bacterial Inactivation. Sci Rep 2016; 6: 20365.
13. Dobrynin D, Wasko K, Friedman G, Fridman A, Fridman G. Cold plasma sterilization of open wounds: Live rat model. Plasma Med 2011; 1: 109-114.
14. Ziuzina D, Boehm D, Patil S, Cullen PJ, Bourke P. Cold plasma inactivation of bacterial biofilms and reduction of quorum sensing regulated virulence factors. PLoS One 2015; 10(9): e0138209.
15. Kim PY, Kim YS, Koo IG, Jung JC, Kim GJ, Choi MY, et al. Bacterial inactivation of wound infection in a human skin model by liquid-phase discharge plasma. PLoS One 2011; 6(8): e24104.
16. Mendes-Oliveira G, Jensen JL, Keener KM, Campanella OH. Modeling the inactivation of Bacillus subtilis spores during cold plasma sterilization. Innov Food Sci Emerg Technol 2019; 52: 334-342.
17. Svarnas P, Spiliopoulou A, Koutsoukos P, Gazeli K, Anastassiou ED. Acinetobacter baumannii deactivation by means of DBD-Based Helium Plasma Jet. Plasma 2019; 2: 77-90.
18. Isbary G, Heinlin J, Shimizu T, Zimmermann JL, Morfill G, Schmidt HU, et al. Successful and safe use of 2 min cold atmospheric argon plasma in chronic wounds: Results of a randomized controlled trial. Br J Dermatol 2012; 167: 404-410.
19. Langner I, Kramer A, Matthes R, Rebert F, Kohler C, Koban I, et al. Inhibition of microbial growth by cold atmospheric plasma compared with the antiseptics chlorhexidine digluconate, octenidine dihydrochloride, and polyhexanide. Plasma Process Polym 2019; 16: 1800162.
20. Turner KH, Everett J, Trivedi U, Rumbaugh KP, Whiteley M. Requirements for Pseudomonas aeruginosa acute burn and chronic surgical wound infection. PLoS Genet 2014; 10(7): e1004518.
21. Xiong Z (2018). Cold Atmospheric Pressure Plasmas (CAPs) for Skin Wound Healing. In: Plasma Medicine - Concepts and Clinical Applications. https://www.intechopen.com/chapters/60721
22. Ermolaeva SA, Varfolomeev AF, Chernukha MY, Yurov DS, Vasiliev MM, Kaminskaya AA, et al. Bactericidal effects of non-thermal argon plasma in vitro, in biofilms and in the animal model of infected wounds. J Med Microbiol 2011; 60: 75-83.
23. Xu G-M, Shi X-M, Cai J-F, Chen S-L, Li P, Yao C-W, et al. Dual effects of atmospheric pressure plasma jet on skin wound healing of mice. Wound Repair Regen 2015; 23: 878-884.
24. Chatraie M, Torkaman G, Khani M, Salehi H, Shokri B. In vivo study of non-invasive effects of non-thermal plasma in pressure ulcer treatment. Sci Rep 2018; 8: 5621.
25. Kubinova S, Zaviskova K, Uherkova L, Zablotskii V, Churpita O, Lunov O, et al. Non-thermal air plasma promotes the healing of acute skin wounds in rats. Sci Rep 2017; 7: 45183.
26. Boekema BKHL, Hofmann S, Van Ham BJT, Bruggeman PJ, Middelkoop E. Antibacterial plasma at safe levels for skin cells. J Phys D Appl Phys 2013; 46: 422001.
27 Boekema BKHL, Vlig M, Guijt D, Hijnen K, Hofmann S, Smits P, et al. A new flexible DBD device for treating infected wounds: In vitro and ex vivo evaluation and comparison with a RF argon plasma jet. J Phys D Appl Phys 2016; 49: 044001.
| Files | ||
| Issue | Vol 17 No 1 (2025) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v17i1.17802 | |
| Keywords | ||
| Cold plasma; Multidrug-resistant; Wound healing antibacterial agents | ||
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How to Cite
1.
Shekari R, Zarrini G, Siahpoush V, Sheikhzadeh Hesari F. Evaluation of cold atmospheric pressure plasma effects on Pseudomonas aeruginosa wound infection in a mouse model. Iran J Microbiol. 2025;17(1):59-68.
