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Sublytic Activity of a Pore-Forming Protein From Commensal Bacteria Causes Epigenetic Modulation of Tumour-Affiliated Protein Expression

Toh, Eric ; Baryalai, Palwasha ; Nadeem, Aftab ; Aung, Kyaw Min ; Myint, Si Lhyam ; Zlatkov, Nikola ; Alidadi, Hadis LU ; Zhu, Shaochun ; Mateus, André and Raina, Deepak Bushan LU , et al. (2025) In Journal of Extracellular Vesicles 14(8).
Abstract

Cytolysin A (ClyA) is a pore-forming protein from a strongly silenced gene in non-pathogenic Escherichia coli, including typical commensal isolates in the intestinal microbiome of healthy mammalian hosts. Upon overproduction, ClyA-expressing bacteria display a cytolytic phenotype. However, it remains unclear whether sublytic amounts of native ClyA play a role in commensal E. coli-host interactions in vivo. Here, we show that sublytic amounts of ClyA are released via outer membrane vesicles (OMVs) and affect host cells in a remarkable manner. OMVs isolated from ClyA+ E. coli were internalised into cultured colon cancer cells. The OMV-associated ClyA caused reduced levels of cancer-activating proteins such as H3K27me3, CXCR4,... (More)

Cytolysin A (ClyA) is a pore-forming protein from a strongly silenced gene in non-pathogenic Escherichia coli, including typical commensal isolates in the intestinal microbiome of healthy mammalian hosts. Upon overproduction, ClyA-expressing bacteria display a cytolytic phenotype. However, it remains unclear whether sublytic amounts of native ClyA play a role in commensal E. coli-host interactions in vivo. Here, we show that sublytic amounts of ClyA are released via outer membrane vesicles (OMVs) and affect host cells in a remarkable manner. OMVs isolated from ClyA+ E. coli were internalised into cultured colon cancer cells. The OMV-associated ClyA caused reduced levels of cancer-activating proteins such as H3K27me3, CXCR4, STAT3 and MDM2 via the EZH2/H3K27me3/microRNA 622/CXCR4 signalling axis. Our results demonstrate that sublytic amounts of ClyA in OMVs from non-pathogenic E. coli can influence the stability of the EZH2 protein, reducing its activity in epigenetic regulation, causing elevated level of the tumour suppressor protein p53.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cancer cell epigenetics, non-pathogenic Escherichia coli, outer membrane vesicles, pore-forming protein cytolysin A
in
Journal of Extracellular Vesicles
volume
14
issue
8
article number
e70149
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:105013631260
  • pmid:40825567
ISSN
2001-3078
DOI
10.1002/jev2.70149
language
English
LU publication?
yes
id
29a61f54-20af-467f-8859-30fd3184d132
date added to LUP
2025-11-07 12:47:19
date last changed
2025-12-19 17:20:44
@article{29a61f54-20af-467f-8859-30fd3184d132,
  abstract     = {{<p>Cytolysin A (ClyA) is a pore-forming protein from a strongly silenced gene in non-pathogenic Escherichia coli, including typical commensal isolates in the intestinal microbiome of healthy mammalian hosts. Upon overproduction, ClyA-expressing bacteria display a cytolytic phenotype. However, it remains unclear whether sublytic amounts of native ClyA play a role in commensal E. coli-host interactions in vivo. Here, we show that sublytic amounts of ClyA are released via outer membrane vesicles (OMVs) and affect host cells in a remarkable manner. OMVs isolated from ClyA<sup>+</sup> E. coli were internalised into cultured colon cancer cells. The OMV-associated ClyA caused reduced levels of cancer-activating proteins such as H3K27me3, CXCR4, STAT3 and MDM2 via the EZH2/H3K27me3/microRNA 622/CXCR4 signalling axis. Our results demonstrate that sublytic amounts of ClyA in OMVs from non-pathogenic E. coli can influence the stability of the EZH2 protein, reducing its activity in epigenetic regulation, causing elevated level of the tumour suppressor protein p53.</p>}},
  author       = {{Toh, Eric and Baryalai, Palwasha and Nadeem, Aftab and Aung, Kyaw Min and Myint, Si Lhyam and Zlatkov, Nikola and Alidadi, Hadis and Zhu, Shaochun and Mateus, André and Raina, Deepak Bushan and Ramstedt, Madeleine and Uhlin, Bernt Eric and Wai, Sun Nyunt}},
  issn         = {{2001-3078}},
  keywords     = {{cancer cell epigenetics; non-pathogenic Escherichia coli; outer membrane vesicles; pore-forming protein cytolysin A}},
  language     = {{eng}},
  number       = {{8}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Journal of Extracellular Vesicles}},
  title        = {{Sublytic Activity of a Pore-Forming Protein From Commensal Bacteria Causes Epigenetic Modulation of Tumour-Affiliated Protein Expression}},
  url          = {{http://dx.doi.org/10.1002/jev2.70149}},
  doi          = {{10.1002/jev2.70149}},
  volume       = {{14}},
  year         = {{2025}},
}