Niacin alleviates cerebral microvascular endothelial cell apoptosis induced by hypervirulent Klebsiella Pneumoniae by reducing the accumulation of reactive oxygen species.

INTRODUCTION

Hypervirulent Klebsiella pneumoniae (hvKp) is an important pathogen causing central nervous system infections, including meningitis; however, the mechanisms by which it disrupts the blood-brain barrier remain unclear. Niacin, a vitamin B3 compound related to NAD+ metabolism, has the potential to regulate redox homeostasis. This study aimed to investigate the mechanism of hvKp-induced injury in human cerebral microvascular endothelial cell (HCMEC) and to evaluate the protective effects of niacin.

METHODS

A GFP-labeled hvKp ATCC 43816 strain was used to establish an HCMEC infection model, and an hvKp mouse meningitis model was also constructed. Live-cell imaging was performed to monitor infection dynamics. Flow cytometry was used to assess infection rate, reactive oxygen species (ROS) levels, and Annexin V-FITC/PI-labeled apoptosis, while Western blotting was used to analyze apoptosis-related pathways. The experimental groups included a control group, an hvKp infection group, an hvKp plus niacin treatment group, and a niacin pretreatment group.

RESULTS

hvKp caused time- and dose-dependent injury to HCMEC, characterized by intracellular proliferation followed by apoptosis induction. Mechanistically, hvKp promoted mitochondrial ROS accumulation and activated the p53-associated mitochondrial apoptotic pathway. Niacin reduced ROS levels, inhibited apoptosis, and alleviated HCMEC injury. In vivo, niacin preserved blood-brain barrier integrity, reduced central nervous system inflammation and hvKp colonization, and improved survival in infected mice.

DISCUSSION: hvKp damages cerebral microvascular endothelial cells and disrupts the blood-brain barrier through the ROS-p53-mitochondrial apoptosis axis. Niacin exerts protective effects by regulating redox homeostasis, suggesting that it may serve as a host-directed adjunctive therapeutic strategy for hvKp-associated central nervous system infections.