Small-molecule inhibitor of HIyU attenuates virulence of Vibrio species

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Title
Small-molecule inhibitor of HIyU attenuates virulence of Vibrio species
Author(s)
Lee, ZW; Kim, BS; Jang, KK; Bang, YJ; Kim, S; Ha, NC; Jung, YH; Lee, HJ; Han, HJ; Jong-Seo Kim; Jeesoo Kim; Sahu, PK; Jeong, LS; Kim, MH; Cho, SH
Publication Date
2019-03
Journal
SCIENTIFIC REPORTS, v.9, no., pp.4346 -
Publisher
NATURE PUBLISHING GROUP
Abstract
Increasing antibiotic resistance has led to the development of new strategies to combat bacterial infection. Anti-virulence strategies that impair virulence of bacterial pathogens are one of the novel approaches with less selective pressure for developing resistance than traditional strategies that impede viability. In this study, a small molecule CM14 [N-(4-oxo-4H-thieno[3,4-c]chromen-3-yl)-3phenylprop-2-ynamide] that inhibits the activity of HIyU, a transcriptional regulator essential for the virulence of the fulminating human pathogen Vibrio vulnificus, has been identified. Without affecting bacterial growth or triggering the host cell death, CM14 reduces HIyU-dependent expression of virulence genes in V. vulnificus. In addition to the decreased hemolysis of human erythrocytes, CM14 impedes host cell rounding and lysis caused by V. vulnificus. Notably, CM14 significantly enhances survival of mice infected with V. vulnificus by alleviating hepatic and renal dysfunction and systemic inflammation. Biochemical, mass spectrometric, and mutational analyses revealed that CM14 inhibits HIyU from binding to target DNA by covalently modifying Cys30. Remarkably, CM14 decreases the expression of various virulence genes of other Vibrio species and thus attenuates their virulence phenotypes. Together, this molecule could be an anti-virulence agent against HIyU-harboring Vibrio species with a low selective pressure for the emergence of resistance. © The Author(s) 2019
URI
https://pr.ibs.re.kr/handle/8788114/6016
ISSN
2045-2322
Appears in Collections:
Center for RNA Research(RNA 연구단) > Journal Papers (저널논문)
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