Understanding plasma biofilm interactions for controlling infection and virulence

Bacterial biofilms are surface adhered communities of bacteria encased within a protective extracellular polymeric matrix. These heterogeneous microbial communities are characterized by elevated tolerance to antimicrobial agents, host immune clearance mechanisms and physical disinfection approaches. Atmospheric pressure non-thermal plasmas have proven to be highly effective in the eradication of bacteria and fungi in both planktonic and biofilm modes of growth at low temperatures, making it a promising approach for surface decontamination of both biotic and abiotic surfaces alike. In addition, non-thermal plasmas as a putative non-antibiotic approach to controlling infectious microorganisms, holds significant promise as an antibiotic alternative infection control strategy, with demonstrated efficacy against antibiotic resistant microorganisms. This topical review introduces the reader to key concepts in biofilm tolerance mechanisms relevant to treatment and control of these surface adhered bacterial communities with cold plasmas. In addition, the ability of plasma-derived active species to interact with both biofilm extracellular matrix components and bacterial cellular targets will be discussed in order to elucidate the mechanisms of antimicrobial and antibiofilm action. By understanding these fundamental interactions, plasma sources may be precisely tailored for antimicrobial applications, specifically for biofilm control where bacterial and fungal physiology (and sensitivity to physical and chemical decontamination) is markedly different from that of their planktonic, or free swimming, counterparts. Recently, novel roles for reactive oxygen and nitrogen species in the activity of conventional antibiotics have been proposed. This extends the possibility that plasmas may enhance the activity of conventional antibiotics and biocides in controlling these highly tolerant microbial populations. Lessons from classical biofilm microbiology can be usefully translated and applied to the design of plasma-based approaches aimed at biofilm control, while potential for tolerance and persistence to plasma in bacterial communities will be reviewed.