Bactericidal, anti-biofilm, and anti-virulence activity of vitamin C against carbapenem-resistant hypervirulent Klebsiella pneumoniae

作者：Xu, Chen; Dong, Ning; Chen, Kaichao; Yang, Xuemei; Zeng, Ping; Hou, Changshun; Chan, Edward Wai Chi; Yao, Xi; Chen, Sheng^*

来源：iScience, 2022, 25(3): 103894.

DOI：10.1016/j.isci.2022.103894

• ASCORBIC-ACID
• ANTIOXIDANT
• INFECTIONS
• PROOXIDANT
• OUTBREAK

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) causing high mortality in clinical patients infers the urgent need for developing therapeutic agents. Here, we demonstrated vitamin C (VC) exhibited strong bactericidal, anti-biofilm, and virulence-suppressing effects on CR-hvKP. Our results showed such a bactericidal effect is dose-dependent both in vitro and in the mouse infection model and is associated with induction of reactive oxygen species (ROS) generation. In addition, VC inhibited biofilm forma tion of CR-hvKP through suppressing the production of exopolysaccharide (EPS). In addition, VC acted as an efflux pump inhibitor at subminimum inhibitory concentration (sub-MIC) to disrupt transportation of EPS and capsular polysaccharide to bacterial cell surface, thereby further inhibiting biofilm and capsule formation. Furthermore, virulence-associated genes in CR-hvKP exposed to sub-MIC of VC were downregulated. Our findings indicated VC could be an effective and safe therapeutic agent to treat CR-hvKP infections in urgent cases when all current treatment options fail.