Novel Plasma Gas-Based Strategy Kills Resistant Bacteria

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Endre J. Szili

A novel, antibiotic-free strategy for fighting antimicrobial-resistant bacteria using cold plasma ionized gas to activate key molecules has shown early efficacy in eradicating bacteria commonly found in chronic wounds such as diabetic foot ulcers. The gas also killed the SARS-CoV-2 virus on surfaces.

"By combining cold plasma gas with acetyl donor molecules to improve its oxidation action, we found [the formulation] completely killed bacteria that are found in chronic wounds," lead author Endre J. Szili said in a press statement on the research, published in Applied Physics Letters.

"We investigated whether this same technology could be effective at killing the SARS-CoV-2 virus and it appears that it is," said Szili, a senior research fellow and head of the Plasma Medicine Research Group at the Future Industries Institute, University of South Australia, Adelaide.

"To the best of knowledge our study is the first report on the use of plasma in combination with acetyl donor molecules," the authors note.

Cold plasma is a low-temperature, electrically generated, partially ionized glow-discharge that is tolerable to human tissue. Although the plasma gas can kill bacteria, the treatment can lose effectiveness against notoriously resistant biofilms.

To try to improve its efficacy in killing bacteria, Szili and colleagues combined the cold plasma with acetyl donor molecules and found the combination generated hydrogen peroxide and released peracetic acid, enhancing the ability to destroy resistant bacteria through a multipronged action.

"The combination of the cold plasma with acetyl donors produces additional oxidants that are less affected by the bacteria's antioxidant defense mechanisms," Szili explained to Medscape Medical News.

The formulation's synergistic effect "can be used to target a broad spectrum of microbes and infectious diseases caused by bacteria, fungi, and viruses," he added.

Gas Killed Bacteria in Foot Ulcers, COVID-19 Virus

For the study, the authors tested the strategy in lab experiments with Pseudomonas aeruginosa, responsible for infections in the blood, lungs, and other areas after surgery, and Staphylococcus aureus, linked to potentially life-threatening blood poisoning and pneumonia.

They found that, while the use of cold plasma alone was effective against P. aeruginosa, it had minimal effect on S. aureus. However, the combination treatment showed successful eradication of both types of bacteria.

"This is very significant for diabetic patients who have foot ulcers that are hard to heal," Szili said in the press statement.

Similar trends were observed when the virucidal activities of the formulation were tested against SARS-CoV-2.

The experiments showed that the plasma-activated blend effectively reduced the SARS-CoV-2 viral load by 50%-84%, raising the possibility of its use in disinfecting surfaces such in hospitals or air-conditioning systems.

"We showed that we could achieve an 84% reduction in viral load using plasma combined with acetyl donor molecules based on a standard dosage that is safe for human cells," Szili said.

"However, it is highly possible with some modifications that we could eradicate it completely."

Working Towards Clinical Trials

A liquid formulation was used in the study, and the authors note that formulations could be configured for on-demand use, potentially as a cream or gel, or even within a hydrogel wound dressing activated by a small hand-held cold plasma device.

Such delivery options can allow for more controlled application of the treatment, Szili said.

"An advantage of our technology is that its delivery can be targeted onto the infected area where needed, as opposed to, for instance, the use of systemic antibiotics," he said.

The technology has also shown potential effects in accelerating wound healing, providing targeted benefits not just specifically where they are needed, but when.

"It might be possible to tailor the formulation to target each stage of wound healing," Szili explained.

"For example, the early stages of healing may require a high dose to clear infection, and once the infection is cleared, a lower dosage can be used to prevent infection and improve the healing process."

Importantly, tailoring treatment timing could also be key in preventing resistance from developing.

"The multipronged action, coupled with on-demand activation prevents prolonged exposure of microorganisms to suboptimal concentrations of the antibacterial agents, all of which are likely to help resist the development of antimicrobial resistance in healthcare and in our environment," he explained.

The research team is currently conducting preclinical trials, with the help of chronic foot wound expert Rob Fitridge, MBBS, of the Royal Adelaide Hospital and Queen Elizabeth Hospital in Australia, to accelerate the technology towards clinical trials for the treatment of chronic wound infections.

"We urgently need an antibiotic-free solution to address the global escalation in antimicrobial resistance and we believe we have made an important first step with this new strategy," Szili said in the press statement.

The proprietary acetyl donor technology is owned by AGA Nanotech of Hertfordshire, UK.

Appl Phys Lett. Published online August 5, 2021. Abstract

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