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

Chen Xu; Ning Dong; Kaichao Chen; Xuemei Yang; Ping Zeng; Changshun Hou; Edward Wai Chi Chan; Xi Yao; Sheng Chen

doi:10.1016/j.isci.2022.103894

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

iScience. 2022 Feb 8;25(3):103894. doi: 10.1016/j.isci.2022.103894. eCollection 2022 Mar 18.

Authors

Chen Xu¹, Ning Dong¹, Kaichao Chen¹, Xuemei Yang¹, Ping Zeng², Changshun Hou³, Edward Wai Chi Chan², Xi Yao³, Sheng Chen¹

Affiliations

¹ Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong.
² State Key Lab of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
³ Department of Biomedical Sciences, City University of Hong Kong, Kowloon, Hong Kong.

Abstract

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 formation 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.

Keywords: Microbiofilms; Microbiology; Molecular biology.