Dihydroartemisinin inhibits plasmid transfer in drug-resistant <i>Escherichia coli</i> via limiting energy supply

Xue-Yang Wang; Huang-Wei Song; Tian Yi; Ying-Bo Shen; Chong-Shan Dai; Cheng-Tao Sun; De-Jun Liu; Jian-Zhong Shen; Cong-Ming Wu; Yang Wang

doi:10.24272/j.issn.2095-8137.2023.084

Volume 44 Issue 5

Sep. 2023

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Article Navigation > Zoological Research > 2023 > 44(5): 894-904

Xue-Yang Wang, Huang-Wei Song, Tian Yi, Ying-Bo Shen, Chong-Shan Dai, Cheng-Tao Sun, De-Jun Liu, Jian-Zhong Shen, Cong-Ming Wu, Yang Wang. Dihydroartemisinin inhibits plasmid transfer in drug-resistant Escherichia coli via limiting energy supply. Zoological Research, 2023, 44(5): 894-904. doi: 10.24272/j.issn.2095-8137.2023.084

Citation:

Xue-Yang Wang, Huang-Wei Song, Tian Yi, Ying-Bo Shen, Chong-Shan Dai, Cheng-Tao Sun, De-Jun Liu, Jian-Zhong Shen, Cong-Ming Wu, Yang Wang. Dihydroartemisinin inhibits plasmid transfer in drug-resistant Escherichia coli via limiting energy supply. Zoological Research, 2023, 44(5): 894-904. doi: 10.24272/j.issn.2095-8137.2023.084

Citation:

Xue-Yang Wang, Huang-Wei Song, Tian Yi, Ying-Bo Shen, Chong-Shan Dai, Cheng-Tao Sun, De-Jun Liu, Jian-Zhong Shen, Cong-Ming Wu, Yang Wang. Dihydroartemisinin inhibits plasmid transfer in drug-resistant Escherichia coli via limiting energy supply. Zoological Research, 2023, 44(5): 894-904. doi: 10.24272/j.issn.2095-8137.2023.084

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Dihydroartemisinin inhibits plasmid transfer in drug-resistant Escherichia coli via limiting energy supply

doi: 10.24272/j.issn.2095-8137.2023.084

Xue-Yang Wang^{1, 2},
Huang-Wei Song^{1, 2},
Tian Yi^{1, 2},
Ying-Bo Shen^{1, 2},
Chong-Shan Dai^{1, 2},
Cheng-Tao Sun^{1, 2},
De-Jun Liu^{1, 2},
Jian-Zhong Shen^{1, 2},
Cong-Ming Wu^{1, 2},
Yang Wang^{1, 2
,
,}

1.
National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
2.
Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 510642, China

All raw RNA-seq data were deposited in the National Center for Biotechnology Information (NCBI) sequence read archive (SRA) under BioProjectID PRJNA971775, Genome Sequence Archive under Accession No. CRA011728, and Science Data Bank under DOI: 10.57760/sciencedb.j00139.00055. All data generated in this study are available within the article and the Supplementary Data files.
Supplementary data to this article can be found online.
The authors declare that they have no competing interests.
The study was conceived and supervised by Y.W. X.Y.W., H.W.S. and T.Y. performed all the experiments. X.Y.W. analyzed the data under the guidance of Y.B.S., C.S.D., C.T.S., D.J.L., C.M.W. and J.Z.S.. Y.W. and X.Y.W. drafted most of the manuscript. All authors read and approved the final version of the manuscript.

Funds: This work was supported in part by grants from the Laboratory of Lingnan Modern Agriculture Project (NT2021006) and National Key Research and Development Program of China (2022YFD1800400)

More Information

Corresponding author: E-mail: wangyang@cau.edu.cn
Received Date: 2023-06-09
Accepted Date: 2023-06-10

Published Online: 2023-07-27

Publish Date: 2023-09-18

Abstract

Abstract

Conjugative transfer of antibiotic resistance genes (ARGs) by plasmids is an important route for ARG dissemination. An increasing number of antibiotic and nonantibiotic compounds have been reported to aid the spread of ARGs, highlighting potential challenges for controlling this type of horizontal transfer. Development of conjugation inhibitors that block or delay the transfer of ARG-bearing plasmids is a promising strategy to control the propagation of antibiotic resistance. Although such inhibitors are rare, they typically exhibit relatively high toxicity and low efficacy in vivo and their mechanisms of action are inadequately understood. Here, we studied the effects of dihydroartemisinin (DHA), an artemisinin derivative used to treat malaria, on conjugation. DHA inhibited the conjugation of the IncI2 and IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 160-fold in vitro in Escherichia coli, and more than two-fold (IncI2 plasmid) in vivo in a mouse model. It also suppressed the transfer of the IncX3 plasmid carrying the carbapenem resistance gene bla_NDM-5 by more than two-fold in vitro. Detection of intracellular adenosine triphosphate (ATP) and proton motive force (PMF), in combination with transcriptomic and metabolomic analyses, revealed that DHA impaired the function of the electron transport chain (ETC) by inhibiting the tricarboxylic acid (TCA) cycle pathway, thereby disrupting PMF and limiting the availability of intracellular ATP for plasmid conjugative transfer. Furthermore, expression levels of genes related to conjugation and pilus generation were significantly down-regulated during DHA exposure, indicating that the transfer apparatus for conjugation may be inhibited. Our findings provide new insights into the control of antibiotic resistance and the potential use of DHA.
- Dihydroartemisinin,
- Plasmid,
- mcr-1,
- bla_NDM-5,
- Conjugation inhibitors,
- TCA cycle

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References(61)

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