Protective Effect of the Golden Staphyloxanthin Biosynthesis Pathway on Staphylococcus aureus under Cold Atmospheric Plasma Treatment.

infection poses a serious threat to public health, and antibiotic resistance has complicated the clinical treatment and limited the solutions available to solve this problem. Cold atmospheric plasma (CAP) is a promising strategy for microorganism inactivation. However, the mechanisms of microbial inactivation or resistance remain unclear. In this study, we treated strains with a self-assembled CAP device and found that CAP can kill in an exposure time-dependent manner. In addition, the liquid environment can influence the survival rate of post-CAP treatment. The cells can be completely inactivated in normal saline and phosphate-buffered saline but not in tryptic soy broth culture medium. Scanning and transmission electron microscopy revealed that the CAP-treated cells maintained integrated morphological structures, similar to the wild-type strain. Importantly, the CAP-treated cells exhibited a reduced pigment phenotype. Deletion of the staphyloxanthin biosynthetic genes and deprived the pigmentation ability of Newman. Both the Newman-Δ and Newman-Δ mutants presented high sensitivity to CAP treatment, whereas Newman-Δ exhibited a survival rate comparable to wild-type Newman after CAP treatment. Our data demonstrated that the yellow pigment intermediates of the staphyloxanthin biosynthetic pathway are responsible for the protection of from CAP inactivation. The key enzymes, such as CrtM and CrtN, of the golden staphyloxanthin biosynthetic pathway could be important targets for the design of novel sterilization strategies against infections. is an important pathogen that can be widely distributed in the community and clinical settings. The emergence of with multiple-antibiotic resistance has complicated staphylococcal infection control. The development of alternative strategies with powerful bactericidal effects is urgently needed. Cold atmospheric plasma (CAP) is a promising strategy for microorganism inactivation. Nevertheless, the underlying mechanisms of microbial inactivation or resistance are not completely illustrated. In this study, we validated the bactericidal effects of CAP on , including antibiotic-resistant strains. We also found that the golden staphyloxanthin, as well as its yellow pigment intermediates, protected against CAP, and blocking the staphyloxanthin synthesis pathway at the early steps could strengthen the sensitivity of to CAP treatment. These data provide insights into the germicidal mechanism of CAP from the aspect of bacteria and suggest new targets against infections.