文章基本信息

标题：Bactericidal, anti-biofilm, and anti-virulence activity of vitamin C against carbapenem-resistant hypervirulent Klebsiella pneumoniae
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作者：Chen Xu ; Ning Dong ; Kaichao Chen 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：3
页码：1-19
DOI：10.1016/j.isci.2022.103894
语种：English
出版社：Elsevier
摘要：SummaryThe emergence of carbapenem-resistant hypervirulentKlebsiella 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 bothin vitroand 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.Graphical abstractDisplay OmittedHighlights•VC exhibited bactericidal and anti-biofilm effects on CR-hvKP•The bactericidal effect of VC is associated with induction of ROS production•VC acted as an efflux pump inhibitor to disrupt transportation of EPS and CPS•VC could suppress the expression of virulence-associated genes in CR-hvKPMolecular biology; Microbiology; Microbiofilms