Helicobacter pylori CagA protein is a potent and broad-spectrum amyloid inhibitor

Zhen Jin; William Pallisgaard Olsen; Cecilia Mörman; Axel Leppert; Rakesh Kumar; Andreas Møllebjerg; Lotte Godthaab Nielsen; Olena V Moshynets; Mykhaylo S Frasinyuk; Jokin Yeregui Elosua; Daniel Ferreira; Axel Abelein; Michael Landreh; Stefan D Knight; Jan Johansson; Daniel E Otzen; Gefei Chen

doi:10.1126/sciadv.ads7525

Helicobacter pylori CagA protein is a potent and broad-spectrum amyloid inhibitor

Zhen Jin, William Pallisgaard Olsen, Cecilia Mörman, Axel Leppert, Rakesh Kumar, Andreas Møllebjerg, Lotte Godthaab Nielsen, Olena V Moshynets, Mykhaylo S Frasinyuk, Jokin Yeregui Elosua, Daniel Ferreira, Axel Abelein, Michael Landreh, Stefan D Knight, Jan Johansson, Daniel E Otzen, Gefei Chen

Interdisciplinary Nanoscience Center

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Bacteria, the smallest and most abundant life forms on Earth, have been a source of insights that have had a considerable impact on human health. Helicobacter pylori has captured substantial attention due to its role in provoking an array of gastrointestinal ailments and other human diseases. Here, we report that H. pylori releases the protein CagA (cytotoxin-associated gene A) that strongly inhibits formation of both functional (bacterial biofilm) and pathogenic amyloid assemblies by targeting various stages during fibril formation. CagA's broad substrate specificity reveals a mechanism whereby H. pylori interferes with other bacteria and humans, offering approaches to combat bacterial infections and human protein misfolding diseases.

Original language	English
Article number	eads7525
Journal	Science Advances
Volume	11
Issue	24
ISSN	2375-2548
DOIs	https://doi.org/10.1126/sciadv.ads7525
Publication status	Published - 13 Jun 2025

Keywords

Antigens, Bacterial/metabolism
Bacterial Proteins/metabolism
Helicobacter pylori/metabolism
Humans
Amyloid/metabolism
Biofilms/growth & development
Helicobacter Infections/microbiology

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Jin, Z., Olsen, W. P., Mörman, C., Leppert, A., Kumar, R., Møllebjerg, A., Nielsen, L. G., Moshynets, O. V., Frasinyuk, M. S., Elosua, J. Y., Ferreira, D., Abelein, A., Landreh, M., Knight, S. D., Johansson, J., Otzen, D. E., & Chen, G. (2025). Helicobacter pylori CagA protein is a potent and broad-spectrum amyloid inhibitor. Science Advances, 11(24), Article eads7525. https://doi.org/10.1126/sciadv.ads7525

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title = "Helicobacter pylori CagA protein is a potent and broad-spectrum amyloid inhibitor",

abstract = "Bacteria, the smallest and most abundant life forms on Earth, have been a source of insights that have had a considerable impact on human health. Helicobacter pylori has captured substantial attention due to its role in provoking an array of gastrointestinal ailments and other human diseases. Here, we report that H. pylori releases the protein CagA (cytotoxin-associated gene A) that strongly inhibits formation of both functional (bacterial biofilm) and pathogenic amyloid assemblies by targeting various stages during fibril formation. CagA's broad substrate specificity reveals a mechanism whereby H. pylori interferes with other bacteria and humans, offering approaches to combat bacterial infections and human protein misfolding diseases. ",

keywords = "Antigens, Bacterial/metabolism, Bacterial Proteins/metabolism, Helicobacter pylori/metabolism, Humans, Amyloid/metabolism, Biofilms/growth & development, Helicobacter Infections/microbiology",

author = "Zhen Jin and Olsen, {William Pallisgaard} and Cecilia M{\"o}rman and Axel Leppert and Rakesh Kumar and Andreas M{\o}llebjerg and Nielsen, {Lotte Godthaab} and Moshynets, {Olena V} and Frasinyuk, {Mykhaylo S} and Elosua, {Jokin Yeregui} and Daniel Ferreira and Axel Abelein and Michael Landreh and Knight, {Stefan D} and Jan Johansson and Otzen, {Daniel E} and Gefei Chen",

year = "2025",

month = jun,

day = "13",

doi = "10.1126/sciadv.ads7525",

language = "English",

volume = "11",

journal = "Science Advances",

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Jin, Z, Olsen, WP, Mörman, C, Leppert, A, Kumar, R, Møllebjerg, A, Nielsen, LG, Moshynets, OV, Frasinyuk, MS, Elosua, JY, Ferreira, D, Abelein, A, Landreh, M, Knight, SD, Johansson, J, Otzen, DE & Chen, G 2025, 'Helicobacter pylori CagA protein is a potent and broad-spectrum amyloid inhibitor', Science Advances, vol. 11, no. 24, eads7525. https://doi.org/10.1126/sciadv.ads7525

TY - JOUR

T1 - Helicobacter pylori CagA protein is a potent and broad-spectrum amyloid inhibitor

AU - Jin, Zhen

AU - Olsen, William Pallisgaard

AU - Mörman, Cecilia

AU - Leppert, Axel

AU - Kumar, Rakesh

AU - Møllebjerg, Andreas

AU - Nielsen, Lotte Godthaab

AU - Moshynets, Olena V

AU - Frasinyuk, Mykhaylo S

AU - Elosua, Jokin Yeregui

AU - Ferreira, Daniel

AU - Abelein, Axel

AU - Landreh, Michael

AU - Knight, Stefan D

AU - Johansson, Jan

AU - Otzen, Daniel E

AU - Chen, Gefei

PY - 2025/6/13

Y1 - 2025/6/13

N2 - Bacteria, the smallest and most abundant life forms on Earth, have been a source of insights that have had a considerable impact on human health. Helicobacter pylori has captured substantial attention due to its role in provoking an array of gastrointestinal ailments and other human diseases. Here, we report that H. pylori releases the protein CagA (cytotoxin-associated gene A) that strongly inhibits formation of both functional (bacterial biofilm) and pathogenic amyloid assemblies by targeting various stages during fibril formation. CagA's broad substrate specificity reveals a mechanism whereby H. pylori interferes with other bacteria and humans, offering approaches to combat bacterial infections and human protein misfolding diseases.

AB - Bacteria, the smallest and most abundant life forms on Earth, have been a source of insights that have had a considerable impact on human health. Helicobacter pylori has captured substantial attention due to its role in provoking an array of gastrointestinal ailments and other human diseases. Here, we report that H. pylori releases the protein CagA (cytotoxin-associated gene A) that strongly inhibits formation of both functional (bacterial biofilm) and pathogenic amyloid assemblies by targeting various stages during fibril formation. CagA's broad substrate specificity reveals a mechanism whereby H. pylori interferes with other bacteria and humans, offering approaches to combat bacterial infections and human protein misfolding diseases.

KW - Antigens, Bacterial/metabolism

KW - Bacterial Proteins/metabolism

KW - Helicobacter pylori/metabolism

KW - Humans

KW - Amyloid/metabolism

KW - Biofilms/growth & development

KW - Helicobacter Infections/microbiology

U2 - 10.1126/sciadv.ads7525

DO - 10.1126/sciadv.ads7525

M3 - Journal article

C2 - 40498838

SN - 2375-2548

VL - 11

JO - Science Advances

JF - Science Advances

IS - 24

M1 - eads7525

ER -

Helicobacter pylori CagA protein is a potent and broad-spectrum amyloid inhibitor

Abstract

Keywords

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