Host CDK-1 and formin mediate microvillar effacement induced by enterohemorrhagic Escherichia coli

Cheng-Rung Huang; Cheng-Ju Kuo; Chih-Wen Huang; Yu-Ting Chen; Bang-Yu Liu; Chung-Ta Lee; Po-Lin Chen; Wen-Tsan Chang; Yun-Wen Chen; Tzer-Min Lee; Hui-Chen Hsieh; Chang-Shi Chen

doi:10.1038/s41467-020-20355-1

Host CDK-1 and formin mediate microvillar effacement induced by enterohemorrhagic Escherichia coli

Nat Commun. 2021 Jan 4;12(1):90. doi: 10.1038/s41467-020-20355-1.

Authors

Cheng-Rung Huang^{1

2}, Cheng-Ju Kuo^{1

2}, Chih-Wen Huang¹, Yu-Ting Chen¹, Bang-Yu Liu¹, Chung-Ta Lee³, Po-Lin Chen^{4

5}, Wen-Tsan Chang^{1

2}, Yun-Wen Chen^{2

6}, Tzer-Min Lee^{7

8}, Hui-Chen Hsieh^{1

2}, Chang-Shi Chen^{9

10}

Affiliations

¹ Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁴ Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁵ Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁶ Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁷ School of Dentistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁸ Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁹ Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. cschen@mail.ncku.edu.tw.
¹⁰ Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. cschen@mail.ncku.edu.tw.

Abstract

Enterohemorrhagic Escherichia coli (EHEC) induces changes to the intestinal cell cytoskeleton and formation of attaching and effacing lesions, characterized by the effacement of microvilli and then formation of actin pedestals to which the bacteria are tightly attached. Here, we use a Caenorhabditis elegans model of EHEC infection to show that microvillar effacement is mediated by a signalling pathway including mitotic cyclin-dependent kinase 1 (CDK1) and diaphanous-related formin 1 (CYK1). Similar observations are also made using EHEC-infected human intestinal cells in vitro. Our results support the use of C. elegans as a host model for studying attaching and effacing lesions in vivo, and reveal that the CDK1-formin signal axis is necessary for EHEC-induced microvillar effacement.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Actins / metabolism
Animals
Caco-2 Cells
Caenorhabditis elegans / metabolism
Caenorhabditis elegans / microbiology
Caenorhabditis elegans / ultrastructure
Caenorhabditis elegans Proteins / metabolism*
Carbohydrate Epimerases / metabolism
Cell Cycle Proteins / metabolism*
Enterohemorrhagic Escherichia coli / pathogenicity
Enterohemorrhagic Escherichia coli / physiology*
Formins
Host-Pathogen Interactions*
Humans
Intestines / microbiology
Microvilli / metabolism
Microvilli / microbiology*
Microvilli / pathology*
Phosphorylation
Phosphothreonine / metabolism
Virulence

Substances

Actins
Caenorhabditis elegans Proteins
Cell Cycle Proteins
Formins
cdk-1 protein, C elegans
Phosphothreonine
ADP-L-glycero-D-mannoheptose-6-epimerase
Carbohydrate Epimerases

Grants and funding

P40 OD010440/OD/NIH HHS/United States