Cold Plasmas for Biofilm Control: Opportunities and Challenges

Abstract

Bacterial biofilm infections account for a major proportion of chronic and medical device associated infections in humans, yet our ability to control them is compromised by their inherent tolerance to antimicrobial agents. Cold atmospheric plasma (CAP) represents a promising therapeutic option. CAP treatment of microbial biofilms represents the convergence of two complex phenomena: the production of a chemically diverse mixture of reactive species and intermediates, and their interaction with a heterogeneous 3D interface created by the biofilm extracellular polymeric matrix. Therefore, understanding these interactions and physiological responses to CAP exposure are central to effective management of infectious biofilms. We review the unique opportunities and challenges for translating CAP to the management of biofilms.

Figure 1.. The Plasma–Biofilm Interface.

The plasma-derived reactive species that diffuse into the biofilm encounter a hydrated, cationic extracellular polymeric matrix which may sequester RONS and attenuate plasma cidal efficacy and maintains a 3D architecture supporting heterogeneous microenvironments that in turn support multispecies microcolonies. Growth rate may be reduced due to nutrient and O₂ limitations within the biofilm, leading to elevated tolerance and persister formation. Quorum sensing, leading to alterations in microbial physiology may also affect microbial tolerance to plasma-derived RONS. Finally, RONS-mediated dispersal of microbes from the biofilm may reverse plasma tolerance. Adapted from [7,87]. Abbreviations: eDNA, extracellular DNA; RONS, reactive oxygen and nitrogen species.

Figure 2.. Schematics of (A) a DBD CAP Source and (B) a CAP Jet Source for Biofilm Eradication and Control.

In A (direct plasma exposure), bacterial biofilm cells are exposed to plasma reactive species, charged particles, high electric fields/current and UV. In B (indirect plasma exposure), bacterial biofilm cells are exposed primarily to reactive oxygen and nitrogen species generated in the plasma afterglow and not the electric fields/current or charged particles. Adapted from [12,26]. Abbreviations: CAP, cold atmospheric plasma; DBD, dielectric barrier discharge.