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

Author(s)

Chen Xu
Ning Dong
Kaichao Chen
Ping Zeng
Edward Wai Chi Chan

Related Research Unit(s)

Detail(s)

Original language	English
Article number	103894
Journal / Publication	iScience
Volume	25
Issue number	3
Online published	8 Feb 2022
Publication status	Published - 18 Mar 2022

Link(s)

DOI	DOI https://doi.org/10.1016/j.isci.2022.103894 Final Published version
	Check@CityULib
Attachment(s)	Documents 96216985.pdf Final Published version, 3.77 MB, PDF Publisher's Copyright Statement This full text is made available under CC-BY-NC-ND 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/
Link to Scopus	https://www.scopus.com/record/display.uri?eid=2-s2.0-85125121337&origin=recordpage
Permanent Link	https://scholars.cityu.edu.hk/en/publications/publication(8a63e9f9-8c0c-4044-bc2f-94ac0b092b0d).html

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.