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Pradimicin U, a promising antimicrobial agent isolated from a newly found Nonomuraea composti sp. nov
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Document Title
Pradimicin U, a promising antimicrobial agent isolated from a newly found Nonomuraea composti sp. nov
Author
Duangupama T., Pittayakhajonwut P., Intaraudom C., Suriyachadkun C., Tadtong S., Kuncharoen N., He Y.-W., Tanasupawat S., Thawai C.
Affiliations
PhD Degree Program in Biology (International Program), Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand; Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, 73170, Thailand; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency, Khlong Luang, Pathum Thani, 12120, Thailand; Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand
Type
Article
Source Title
Scientific Reports
ISSN
20452322
Year
2024
Volume
14
Issue
1
Open Access
All Open Access, Gold
Publisher
Nature Research
DOI
10.1038/s41598-024-58834-w
Abstract
Infections with dengue virus (DENV) remain a worldwide public health problem. A number of bona fide cellular targets of DENV have been identified including liver cells. Despite the many lines of evidence confirming the involvement of hepatocytes during DENV infection, only a few studies have used proteomic analysis to understand the modulation of the cellular proteome occurring upon DENV infection. We utilized a 2D-gel electrophoresis analysis to identify proteins that were differentially regulated by DENV 2 infection of liver (Hep3B) cells at 12 h post infection (hpi) and at 48 hpi. The analysis identifies 4 proteins differentially expressed at 12 hpi, and 14 differentially regulated at 48 hpi. One candidate protein identified as downregulated at 48 hpi in the proteomic analysis (GAPDH) was validated in western blotting in Hep3B cells, and subsequently in induced pluripotent stem cell (iPSC) derived human hepatocytes. The reduced expression of GAPDH was coupled with an increase in NADH, and a significantly reduced NAD + /NADH ratio, strongly suggesting that glycolysis is down regulated in response to DENV 2 infection. Metformin, a well characterized drug used in the treatment of diabetes mellitus, is an inhibitor of hepatic gluconeogenesis was shown to reduce the level of DENV 2 infection and new virus production. Collectively these results show that although glycolysis is reduced, glucose is still required, possibly for use by the pentose phosphate pathway to generate nucleosides required for viral replication. ? The Author(s) 2024.
License
CC BY
Rights
Authors
Publication Source
WoS