Anthocyanin Extract from Purple Sweet Potato Exacerbate Mitophagy to Ameliorate Pyroptosis in Klebsiella pneumoniae Infection.

Guokai Dong,Jinjuan Liu,Huimin Bu,Meng Wang,Fei Jiang,Rongpeng Li,Nana Xu,Yunyun Zhao,Bo Yuan

doi:10.3390/ijms222111422

Abstract

Given the rise of morbidity and mortality caused by Klebsiella pneumoniae (KP), the increasing number of strains resistant to antibiotics, and the emergence of hypervirulent Klebsiella pneumonia, treatment of KP infection becomes difficult; thus, novel drugs are necessary for treatment. Anthocyanins, or natural flavonoids, have an extensive effect against bacterial infection. However, few studies on anti-KP are identified. Here, we evaluated the therapeutic effect of purple sweet potato anthocyanins (PSPAs) on KP, containing 98.7% delphinidin 3-sambubioside. Results showed that KP-infected mice after PSPAs treatment manifested decreased mortality, weakened lung injury, dampened inflammatory responses, and reduced bacterial systemic dissemination in vivo. In Vitro, PSPAs significantly suppressed pyroptosis and restricted NLRP3 inflammasome activation in alveolar macrophages infected with KP. As for the mechanism, PSPAs promote mitophagy by recruiting Parkin to the mitochondria. PSPAs-conferred mitophagy increased mitochondrial membrane potential and decreased mitochondrial reactive oxygen species and mitochondrial DNA, resulting in impaired NLRP3 inflammasome activation. In addition, the promotion of mitophagy by PSPAs required the Nrf2 signaling pathway. Collectively, these findings suggest that PSPAs are a potential option for the treatment of KP infection.

Highlights

Klebsiella pneumoniae (KP), singled out as an “urgent threat to human health”, is an opportunistic bacterial pathogen causing a variety of infectious diseases that are often difficult to treat, including pneumonia, bacteremia, urinary tract infections, and liver abscesses [1]
We found that bacterial CFUs in the lungs and bronchoalveolar lavage fluid (BALF) of purple sweet potato anthocyanins (PSPAs)-treated mice were significantly lower than that of control mice (Figure 1C,D)
These results suggested that PSPAs contributed to the host defense against KP in pneumonia models

Summary

Introduction

Klebsiella pneumoniae (KP), singled out as an “urgent threat to human health”, is an opportunistic bacterial pathogen causing a variety of infectious diseases that are often difficult to treat, including pneumonia, bacteremia, urinary tract infections, and liver abscesses [1]. In China, KP, which is composed of 11.9% of pathogens, is isolated from ventilator-associated pneumonia and ICU-acquired pneumonia [4]. Another feature of these infections is the increasing number of strains resistant to antibiotics. By one count, this pathogen accounts for 73.9% of carbapenemresistant Enterobacteriaceae [5]. The emergence of hypervirulent Klebsiella pneumoniae and the spread of carbapenem-resistant hypervirulent Klebsiella colonization in ICU COVID-19 patients pose a great challenge to public health [6]. The great serotype variability requires either high-valency vaccines or monoclonal antibody cocktails to obtain acceptable coverage. New therapeutic agents are necessary to improve outcomes in patients with KP

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