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In vitro and in vivo activities of scutellarein, a novel polyphosphate kinase 1 inhibitor against Acinetobacter baumannii infection

Authors :
Yuping Song
Hongfa Lv
Lei Xu
Zhiying Liu
Jianfeng Wang
Tianqi Fang
Xuming Deng
Yonglin Zhou
Dan Li
Source :
Microbial Cell Factories, Vol 23, Iss 1, Pp 1-14 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

Abstract Background Inorganic polyphosphate (polyP)-targeted polyphosphate kinase 1 (PPK1) has attracted much attention by virtue of its importance in bacterial pathogenicity and persistence, as well as its exclusive presence in microorganisms. However, only very few drugs have been found to be efficacious in inhibiting the Acinetobacter baumannii (A. baumannii) PPK1 protein. Results In this study, we identified Scutellarein (Scu), a potent PPK1 inhibitor that could significantly influence PPK1-regulated motility, biofilm formation, and bacterial persistence, which was further validated by the results of transcriptome analysis. Mechanistic explorations revealed that Scu achieved its enzyme inhibitory activity predominantly through direct engagement with the active center of PPK1. Moreover, the survival rate of Galleria mellonella larvae was increased by about 35% with 20 mg/kg of Scu treatment. The remarkable therapeutic benefits of Scu were also observed in the mouse pneumonia model, shown mainly by reduced bacterial colonization, pathological lesions, and inflammatory factors. Conclusion Our results revealed that Scu could attenuate the pathogenicity and persistence of A. baumannii by interfering with its important kinase PPK1.

Details

Language :
English
ISSN :
14752859
Volume :
23
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Microbial Cell Factories
Publication Type :
Academic Journal
Accession number :
edsdoj.2b23e73b4845d1b3fa3c8068e0695e
Document Type :
article
Full Text :
https://doi.org/10.1186/s12934-024-02540-9