The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern. However, no specific antiviral treatments or vaccines are available yet. This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2.

Bacterial extracellular vesicles (EVs) are natural reservoirs of biological active substances. They exhibit promising application in developing bioproducts such as vaccine, drug‐delivery system and anticancer agent. However, the low yield of naturally secreted EVs during bacterial growth is a bottleneck factor that restricts EV applications. In this study, we showed that sub‐minimum inhibitory concentration (MIC) of β‐lactams boosted EV production in various Staphylococcus aureus strains. The expression of penicillin‐binding protein (PBP) genes increased after β‐lactam treatment, and the inactivation of alternative PBPs promoted EV secretion of S. aureus. We also demonstrated that sub‐MIC β‐lactams promoted EV production via a reactive oxygen species (ROS)‐dependent pathway. Deletion of redundant pbp genes enhanced oxacillin (OXA)‐stimulated ROS levels. Transcriptomic and lipidomic analyses revealed that OXA‐induced ROS triggered lipid metabolic reprogramming in S. aureus. Particularly, ROS promoted lipid peroxidation (LPO) and increased the biosynthesis of phosphatidic acid (PA) and lipoteichoic acid (LTA) that contributed to EV generation. Furthermore, OXA treatment altered the diversity of EV‐loaded proteins. OXA‐treated ^∆agr/OXAEVs induced stronger Dengue EDIII‐specific antibodies in BALB/c mice than did ^∆agrEVs. Overall, this study provided mechanic insights into β‐lactam‐promoted EV production in S. aureus, and highlighted the potential strategies to prepare EVs for various applications.

Antimicrobial resistance (AMR), especially in clinically important bacteria, has posed serious challenges to clinical treatments. Novel and effective antimicrobial strategies are urgently needed to address AMR. Cold atmospheric plasma (CAP) is a new concept of disinfection method that kills bacteria through various active species and particles within an ionised and electrical‐balanced gas. In this review, we introduced the generation of CAP and summarised its disinfection mechanisms. Moreover, we reviewed the applications of CAP in treating globally important bacteria, including Gram‐positive bacteria such as Staphylococcus aureus , Enterococcus spp., Streptococcus pyogenes and Mycobacterium tuberculosis , as well as Gram‐negative bacteria including Escherichia coli , Pseudomonas aeruginosa , Klebsiella pneumoniae , Acinetobacter baumannii and Neisseria gonorrhoeae . Additionally, we discussed technological strategies to enhance CAP disinfection efficacy and evaluated the safety of CAP applications. We recommend CAP as an effective alternative technology for combating bacterial infections and hope that the comprehensive information provided in the present review will facilitate the development of CAP‐based disinfection strategies to overcome AMR issues in the future.

Staphylococcus aureus is a vital pathogen causing clinical infections. Capsules are important virulence factors for S. aureus. This study investigates the regulatory mechanisms underlying capsule production in S. aureus. Bacterial strains XN108 and Newman were used, and combined approaches like RNA sequencing (RNA-seq), RT-qPCR, transmission electron microscopy (TEM), gene reporter, and electrophoretic mobility shift assay (EMSA) were performed to test the role and mechanism of WalK(S221P) mutation in S. aureus capsule production. RNA-seq showed an increased expression of cap genes in the WalK(S221P)-carried S. aureus XN108 relative to the mutation-cured XN108-R. TEM and capsular polysaccharide determination demonstrated that XN108 produced more capsules than XN108-R did. Similar results were presented in the WalK(S221P)-contained K-Newman versus the wild-type Newman. RT-qPCR screening showed an increasing expression of the mgrA gene in XN108 versus XN108-R. Gene reporter and EMSA analysis revealed that WalK(S221P) mutation promoted S. aureus capsule production through MgrA. Deletion of mgrA decreased the WalK(S221P)-mediated capsule yield. Moreover, WalK(S221P) mutation remarkably increased the tolerance of S. aureus to whole blood killing and microphage phagocytosis. Overall, these data provide mechanistic insights into the effect of WalK(S221P) on the capsule production of S. aureus, which may set down foundations for future S. aureus virulence investigations.

Antibiotic-resistant Staphylococcus aureus infections pose a formidable clinical challenge. Cold atmospheric plasma (CAP) has emerged as a promising disinfection technology; however, the underlying bacterial response mechanisms and potential resistance to CAP remain incompletely elucidated. Here, we validated the broad-spectrum and efficient bactericidal activity of CAP against both drug-sensitive and drug-resistant clinical isolates of S. aureus. Mechanistically, CAP primarily eliminated bacteria by inducing oxidative damage to proteins and lipids, thereby disrupting internal cellular structures. The addition of exogenous free radical scavengers significantly attenuated CAP-mediated oxidative killing. Transcriptomic analysis and RT-qPCR validation further revealed upregulation of redox-related genes in S. aureus following CAP exposure. Deletion of key antioxidant genes, particularly ahpC and mrgA, markedly enhanced bacterial susceptibility to CAP. Virtual screening and surface plasmon resonance analysis identified two small-molecular inhibitors, C4515 and A8226, which specifically target AhpC and MrgA, respectively, and potentiated CAP bactericidal efficacy. Collectively, this study delineates the molecular interactions between CAP and S. aureus, and underscores the potential of CAP-based strategies for combating drug-resistant bacterial infections.