Cold atmospheric plasma for the enhancement of antimicrobial strategies against bacterial biofilms

The kHz-driven jet proved superior for biofilm eradication, offering insights into enhancement of antimicrobial efficacy against tolerant infections. Chapter4 focuses on Pseudomonas aeruginosa, which forms robust, highly tolerant biofilms. Planktonic and biofilm P. aeruginosa samples were sub-lethally exposed using a kHz drivenjet.

While planktonic bacteria were almost eradicated after 120 sec CAP exposures, biofilm eradication required longer treatments. Transcriptomic analyses revealkey responses to sub-lethal plasma exposure, including upregulation of oxidative stress response genes and evidence of CAP-induced membrane disturbances. Thischapter documents the first example of CAP-induced stringent response in P. aeruginosa, offering mechanistic insights.

Chapter 5 utilises an alginate bead biofilm modelto investigate CAP effects on antibiotic-biofilm matrix interactions. CAP-enhanced biofilm penetration by the cationic antibiotic tobramycin was observed, due to reducedinteractions with the extracellular matrix. Changes to P. aeruginosa virulence factor production suggests the potential for reducing biofilm defences and improving antimicrobial effectiveness.

The thesis emphasises CAP's potential as a complementary strategy to synergise antibiotic activity and disrupt biofilms. The findings provide insight into CAP mechanisms of action and highlight the need to standardise treatments to ensure safety and efficacy of future clinical applications.<br><br><i>Thesis is embargoed until 31 December 2030.</i>