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

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.

SUBMITTER: Dong G

PROVIDER: S-EPMC8583717 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In various plant species, many transcription factors (TFs), such as MYB, bHLH, and WD40, have been identified as regulators of anthocyanin biosynthesis in underground organs. However, the regulatory elements of anthocyanin biosynthesis in the tuberous roots of sweet potato have not been elucidated yet. Here, we selected the purple-fleshed sweet potato cultivar "Zhezi1" (ZZ P ) and its spontaneous yellow-fleshed mutant "Xinli" (XL Y ) to investigate the regulatory mechanism of the anthocyanin biosynthesis in the tuberous roots of sweet potato. By analyzing the IbMYB1 genotype in ZZ P and XL Y , we found that the IbMYB1-2, a MYB TF involved in anthocyanin biosynthesis, was missing in the XL Y genome, which might lead to an extreme decrease in anthocyanins in XL Y . A comparative transcriptome analysis of ZZ P and XL Y was conducted to find the TFs involved in anthocyanin biosynthesis in ZZ P and XL Y . The anthocyanin structural genes were significantly enriched among the differentially expressed genes. Moreover, one MYB activator (IbMYB1), one bHLH (IbbHLH2), three WRKY activator candidates (IbWRKY21, IbWRKY24, and IbWRKY44), and two MYB repressors (IbMYB27 and IbMYBx-ZZ) were highly expressed in ZZ P accompanied with anthocyanin structural genes. We also tested the expression of these TFs in six purple- and two orange-fleshed sweet potato cultivars. Interestingly, most of these TFs were significantly positively correlated with anthocyanin contents in these cultivars. The function of the anthocyanin biosynthesis repression of IbMYB27 and IbMYBx-ZZ was verified through transient co-transformation with IbMYB1 into tobacco leaves. Further functional verification of the above TFs was conducted by Y2H, BiFC, and dual-luciferase assays. These tests showed that the MYB-bHLH-WD40/MYB-bHLH-WD40-WRKY complex activated the promoter of anthocyanin structural gene IbDFR and promoters for IbWRKY44, IbMYB27, and IbMYBx-ZZ, indicating reinforcement and feedback regulation to maintain the level of anthocyanin accumulation in the tuberous roots of purple-fleshed sweet potato. These results may provide new insights into the regulatory mechanism of anthocyanin biosynthesis and accumulation in underground organs of sweet potatoes.

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

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