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Use of Modified Clostridium perfringens Enterotoxin Fragments for Claudin Targeting in Liver and Skin Cells

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Use of Modified Clostridium perfringens Enterotoxin Fragments for Claudin Targeting in Liver and Skin Cells. / Beier, Laura-Sophie; Rossa, Jan; Woodhouse, Stephen; Bergmann, Sophia; Kramer, Holger B; Protze, Jonas; Eichner, Miriam; Piontek, Anna; Vidal-Y-Sy, Sabine; Brandner, Johanna M; Krause, Gerd; Zitzmann, Nicole; Piontek, Jörg.

In: INT J MOL SCI, Vol. 20, No. 19, 26.09.2019.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Beier, L-S, Rossa, J, Woodhouse, S, Bergmann, S, Kramer, HB, Protze, J, Eichner, M, Piontek, A, Vidal-Y-Sy, S, Brandner, JM, Krause, G, Zitzmann, N & Piontek, J 2019, 'Use of Modified Clostridium perfringens Enterotoxin Fragments for Claudin Targeting in Liver and Skin Cells', INT J MOL SCI, vol. 20, no. 19. https://doi.org/10.3390/ijms20194774

APA

Beier, L-S., Rossa, J., Woodhouse, S., Bergmann, S., Kramer, H. B., Protze, J., Eichner, M., Piontek, A., Vidal-Y-Sy, S., Brandner, J. M., Krause, G., Zitzmann, N., & Piontek, J. (2019). Use of Modified Clostridium perfringens Enterotoxin Fragments for Claudin Targeting in Liver and Skin Cells. INT J MOL SCI, 20(19). https://doi.org/10.3390/ijms20194774

Vancouver

Beier L-S, Rossa J, Woodhouse S, Bergmann S, Kramer HB, Protze J et al. Use of Modified Clostridium perfringens Enterotoxin Fragments for Claudin Targeting in Liver and Skin Cells. INT J MOL SCI. 2019 Sep 26;20(19). https://doi.org/10.3390/ijms20194774

Bibtex

@article{58dfca8c37e1476d804eb992dd66027e,
title = "Use of Modified Clostridium perfringens Enterotoxin Fragments for Claudin Targeting in Liver and Skin Cells",
abstract = "Claudins regulate paracellular permeability in different tissues. The claudin-binding domain of Clostridium perfringens enterotoxin (cCPE) is a known modulator of a claudin subset. However, it does not efficiently bind to claudin-1 (Cldn1). Cldn1 is a pharmacological target since it is (i) an essential co-receptor for hepatitis C virus (HCV) infections and (ii) a key element of the epidermal barrier limiting drug delivery. In this study, we investigated the potential of a Cldn1-binding cCPE mutant (i) to inhibit HCV entry into hepatocytes and (ii) to open the epidermal barrier. Inhibition of HCV infection by blocking of Cldn1 with cCPE variants was analyzed in the Huh7.5 hepatoma cell line. A model of reconstructed human epidermis was used to investigate modulation of the epidermal barrier by cCPE variants. In contrast to cCPEwt, the Cldn1-binding cCPE-S305P/S307R/S313H inhibited infection of Huh7.5 cells with HCV in a dose-dependent manner. In addition, TJ modulation by cCPE variant-mediated targeting of Cldn1 and Cldn4 opened the epidermal barrier in reconstructed human epidermis. cCPE variants are potent claudin modulators. They can be applied for mechanistic in vitro studies and might also be used as biologics for therapeutic claudin targeting including HCV treatment (host-targeting antivirals) and improvement of drug delivery.",
keywords = "Amino Acid Substitution, Cell Line, Tumor, Claudins/chemistry, Enterotoxins/chemistry, Epidermis/metabolism, Hepacivirus/drug effects, Hepatitis C/metabolism, Hepatocytes/metabolism, Humans, Models, Molecular, Molecular Conformation, Protein Binding, Skin/cytology, Virus Internalization/drug effects, Virus Replication",
author = "Laura-Sophie Beier and Jan Rossa and Stephen Woodhouse and Sophia Bergmann and Kramer, {Holger B} and Jonas Protze and Miriam Eichner and Anna Piontek and Sabine Vidal-Y-Sy and Brandner, {Johanna M} and Gerd Krause and Nicole Zitzmann and J{\"o}rg Piontek",
year = "2019",
month = sep,
day = "26",
doi = "10.3390/ijms20194774",
language = "English",
volume = "20",
journal = "INT J MOL SCI",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "19",

}

RIS

TY - JOUR

T1 - Use of Modified Clostridium perfringens Enterotoxin Fragments for Claudin Targeting in Liver and Skin Cells

AU - Beier, Laura-Sophie

AU - Rossa, Jan

AU - Woodhouse, Stephen

AU - Bergmann, Sophia

AU - Kramer, Holger B

AU - Protze, Jonas

AU - Eichner, Miriam

AU - Piontek, Anna

AU - Vidal-Y-Sy, Sabine

AU - Brandner, Johanna M

AU - Krause, Gerd

AU - Zitzmann, Nicole

AU - Piontek, Jörg

PY - 2019/9/26

Y1 - 2019/9/26

N2 - Claudins regulate paracellular permeability in different tissues. The claudin-binding domain of Clostridium perfringens enterotoxin (cCPE) is a known modulator of a claudin subset. However, it does not efficiently bind to claudin-1 (Cldn1). Cldn1 is a pharmacological target since it is (i) an essential co-receptor for hepatitis C virus (HCV) infections and (ii) a key element of the epidermal barrier limiting drug delivery. In this study, we investigated the potential of a Cldn1-binding cCPE mutant (i) to inhibit HCV entry into hepatocytes and (ii) to open the epidermal barrier. Inhibition of HCV infection by blocking of Cldn1 with cCPE variants was analyzed in the Huh7.5 hepatoma cell line. A model of reconstructed human epidermis was used to investigate modulation of the epidermal barrier by cCPE variants. In contrast to cCPEwt, the Cldn1-binding cCPE-S305P/S307R/S313H inhibited infection of Huh7.5 cells with HCV in a dose-dependent manner. In addition, TJ modulation by cCPE variant-mediated targeting of Cldn1 and Cldn4 opened the epidermal barrier in reconstructed human epidermis. cCPE variants are potent claudin modulators. They can be applied for mechanistic in vitro studies and might also be used as biologics for therapeutic claudin targeting including HCV treatment (host-targeting antivirals) and improvement of drug delivery.

AB - Claudins regulate paracellular permeability in different tissues. The claudin-binding domain of Clostridium perfringens enterotoxin (cCPE) is a known modulator of a claudin subset. However, it does not efficiently bind to claudin-1 (Cldn1). Cldn1 is a pharmacological target since it is (i) an essential co-receptor for hepatitis C virus (HCV) infections and (ii) a key element of the epidermal barrier limiting drug delivery. In this study, we investigated the potential of a Cldn1-binding cCPE mutant (i) to inhibit HCV entry into hepatocytes and (ii) to open the epidermal barrier. Inhibition of HCV infection by blocking of Cldn1 with cCPE variants was analyzed in the Huh7.5 hepatoma cell line. A model of reconstructed human epidermis was used to investigate modulation of the epidermal barrier by cCPE variants. In contrast to cCPEwt, the Cldn1-binding cCPE-S305P/S307R/S313H inhibited infection of Huh7.5 cells with HCV in a dose-dependent manner. In addition, TJ modulation by cCPE variant-mediated targeting of Cldn1 and Cldn4 opened the epidermal barrier in reconstructed human epidermis. cCPE variants are potent claudin modulators. They can be applied for mechanistic in vitro studies and might also be used as biologics for therapeutic claudin targeting including HCV treatment (host-targeting antivirals) and improvement of drug delivery.

KW - Amino Acid Substitution

KW - Cell Line, Tumor

KW - Claudins/chemistry

KW - Enterotoxins/chemistry

KW - Epidermis/metabolism

KW - Hepacivirus/drug effects

KW - Hepatitis C/metabolism

KW - Hepatocytes/metabolism

KW - Humans

KW - Models, Molecular

KW - Molecular Conformation

KW - Protein Binding

KW - Skin/cytology

KW - Virus Internalization/drug effects

KW - Virus Replication

U2 - 10.3390/ijms20194774

DO - 10.3390/ijms20194774

M3 - SCORING: Journal article

C2 - 31561440

VL - 20

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 19

ER -