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

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

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

32 Citations (Scopus)

57 Downloads (CityUHK Scholars)

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.

Original language	English
Article number	103894
Journal	iScience
Volume	25
Issue number	3
Online published	8 Feb 2022
DOIs	https://doi.org/10.1016/j.isci.2022.103894
Publication status	Published - 18 Mar 2022

Funding

This research was supported by the Research Impact Fund (R5011-18F) of the Hong Kong Research Grant Council.

Research Keywords

Microbiofilms
Microbiology
Molecular biology

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/

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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

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",

author = "Chen Xu and Ning Dong and Kaichao Chen and Xuemei Yang and Ping Zeng and Changshun Hou and {Chi Chan}, {Edward Wai} and Xi Yao and Sheng Chen",

year = "2022",

month = mar,

day = "18",

doi = "10.1016/j.isci.2022.103894",

language = "English",

volume = "25",

number = "3",

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TY - JOUR

T1 - Bactericidal, anti-biofilm, and anti-virulence activity of vitamin C against carbapenem-resistant hypervirulent Klebsiella pneumoniae

AU - Xu, Chen

AU - Dong, Ning

AU - Chen, Kaichao

AU - Yang, Xuemei

AU - Zeng, Ping

AU - Hou, Changshun

AU - Chi Chan, Edward Wai

AU - Yao, Xi

AU - Chen, Sheng

PY - 2022/3/18

Y1 - 2022/3/18

N2 - 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.

AB - 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.

KW - Microbiofilms

KW - Microbiology

KW - Molecular biology

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U2 - 10.1016/j.isci.2022.103894

DO - 10.1016/j.isci.2022.103894

M3 - RGC 21 - Publication in refereed journal

C2 - 35243252

SN - 2589-0042

VL - 25

JO - iScience

JF - iScience

IS - 3

M1 - 103894

ER -

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

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

UN SDGs

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RIF: Development of a Colistin/Adjuvant Antimicrobial Regimen That Exhibits Low Toxicity and High Efficacy in Combating Multi-drug-resistant Bacterial Pathogens

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

Abstract

Funding

Research Keywords

Publisher's Copyright Statement

UN SDGs

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Other Access Options

Permanent Link

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RIF: Development of a Colistin/Adjuvant Antimicrobial Regimen That Exhibits Low Toxicity and High Efficacy in Combating Multi-drug-resistant Bacterial Pathogens

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