Mechanisms of bacterial inhibition and tolerance around cold atmospheric plasma

Abstract

The grim situation of bacterial infection has undoubtedly become a major threat to human health. In the context of frequent use of antibiotics, a new bactericidal method is urgently needed to fight against drug-resistant bacteria caused by non-standard use of antibiotics. Cold atmospheric plasma (CAP) is composed of a variety of bactericidal species, which has excellent bactericidal effect on microbes. However, the mechanism of interaction between CAP and bacteria is not completely clear. In this paper, we summarize the mechanisms of bacterial killing by CAP in a systematic manner, discuss the responses of bacteria to CAP treatment that are considered to be related to tolerance and their underlying mechanisms, review the recent advances in bactericidal applications of CAP finally. This review indicates that CAP inhibition and tolerance of survival bacteria are a set of closely related mechanisms and suggests that there might be other mechanisms of tolerance to survival bacteria that had not been discovered yet. In conclusion, this review shows that CAP has complex and diverse bactericidal mechanisms, and has excellent bactericidal effect on bacteria at appropriate doses. KEY POINTS: • The bactericidal mechanism of CAP is complex and diverse. • There are few resistant bacteria but tolerant bacteria during CAP treatment. • There is excellent germicidal effect when CAP in combination with other disinfectants.

Keywords: Bacterial resistance; Bacterial tolerance; Bactericidal application; Biofilm; Cold atmospheric plasma.

Fig. 1

Mechanism of action between CAP and planktonic bacteria. a Perforation of cell membrane induced by ROS and RNS. b Leakage of proteins and DNA in the cell through the pores. c Breakage of nucleotide chains caused by oxidative stress. d Modifications of proteins promote the formation of protein–protein cross-links. e Destruction of proteins structure induced by CAP. f Bacteria fight against ROS and RNS mainly through antioxidant enzymes. g Bacteria prevent the formation of protein–protein cross-links through head shock proteins. Black spots represent ROS and RNS in the CAP

Fig. 2

Mechanism of action between CAP and biofilm. At low-doses of CAP, a the outer structure of biofilm is slightly damaged, b QS signaling molecules are not significantly affected, c persisters are induced to form in biofilms, and d ROS is restricted in the biofilm surface. At high-dose of CAP, e the outer structure of biofilm is seriously damaged, f QS signaling molecules are destroyed, g the bacterial structure in the biofilm is seriously damaged, and h ROS diffuses to the deep layer of biofilm. Green spots represent ROS and RNS in the CAP. Purple triangles represent QS signaling molecules. Gray ellipses represent bacteria in biofilm. Green ellipses represent persister cells