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Sublytic Activity of a Pore‐Forming Protein From Commensal Bacteria Causes Epigenetic Modulation of Tumour‐Affiliated Protein Expression
by
Mateus, André
, Alidadi, Hadis
, Myint, Si Lhyam
, Baryalai, Palwasha
, Wai, Sun Nyunt
, Toh, Eric
, Uhlin, Bernt Eric
, Aung, Kyaw Min
, Zlatkov, Nikola
, Zhu, Shaochun
, Ramstedt, Madeleine
, Raina, Deepak Bushan
, Nadeem, Aftab
in
Basic Medicine
/ cancer cell epigenetics
/ Cell Line, Tumor
/ Colonic Neoplasms - genetics
/ Colonic Neoplasms - metabolism
/ Enhancer of Zeste Homolog 2 Protein - genetics
/ Enhancer of Zeste Homolog 2 Protein - metabolism
/ Epigenesis, Genetic
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - metabolism
/ Extracellular Vesicles - metabolism
/ Gastrointestinal Microbiome
/ Hemolysin Proteins - metabolism
/ Histones - metabolism
/ Humans
/ Medical and Health Sciences
/ Medicin och hälsovetenskap
/ Medicinska och farmaceutiska grundvetenskaper
/ Microbiology in the Medical Area
/ MicroRNAs - metabolism
/ Mikrobiologi inom det medicinska området
/ non-pathogenic Escherichia coli
/ Original
/ outer membrane vesicles
/ pore-forming protein cytolysin A
/ Receptors, CXCR4 - metabolism
/ Signal Transduction
/ STAT3 Transcription Factor - metabolism
/ Tumor Suppressor Protein p53 - metabolism
2025
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Sublytic Activity of a Pore‐Forming Protein From Commensal Bacteria Causes Epigenetic Modulation of Tumour‐Affiliated Protein Expression
by
Mateus, André
, Alidadi, Hadis
, Myint, Si Lhyam
, Baryalai, Palwasha
, Wai, Sun Nyunt
, Toh, Eric
, Uhlin, Bernt Eric
, Aung, Kyaw Min
, Zlatkov, Nikola
, Zhu, Shaochun
, Ramstedt, Madeleine
, Raina, Deepak Bushan
, Nadeem, Aftab
in
Basic Medicine
/ cancer cell epigenetics
/ Cell Line, Tumor
/ Colonic Neoplasms - genetics
/ Colonic Neoplasms - metabolism
/ Enhancer of Zeste Homolog 2 Protein - genetics
/ Enhancer of Zeste Homolog 2 Protein - metabolism
/ Epigenesis, Genetic
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - metabolism
/ Extracellular Vesicles - metabolism
/ Gastrointestinal Microbiome
/ Hemolysin Proteins - metabolism
/ Histones - metabolism
/ Humans
/ Medical and Health Sciences
/ Medicin och hälsovetenskap
/ Medicinska och farmaceutiska grundvetenskaper
/ Microbiology in the Medical Area
/ MicroRNAs - metabolism
/ Mikrobiologi inom det medicinska området
/ non-pathogenic Escherichia coli
/ Original
/ outer membrane vesicles
/ pore-forming protein cytolysin A
/ Receptors, CXCR4 - metabolism
/ Signal Transduction
/ STAT3 Transcription Factor - metabolism
/ Tumor Suppressor Protein p53 - metabolism
2025
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Sublytic Activity of a Pore‐Forming Protein From Commensal Bacteria Causes Epigenetic Modulation of Tumour‐Affiliated Protein Expression
by
Mateus, André
, Alidadi, Hadis
, Myint, Si Lhyam
, Baryalai, Palwasha
, Wai, Sun Nyunt
, Toh, Eric
, Uhlin, Bernt Eric
, Aung, Kyaw Min
, Zlatkov, Nikola
, Zhu, Shaochun
, Ramstedt, Madeleine
, Raina, Deepak Bushan
, Nadeem, Aftab
in
Basic Medicine
/ cancer cell epigenetics
/ Cell Line, Tumor
/ Colonic Neoplasms - genetics
/ Colonic Neoplasms - metabolism
/ Enhancer of Zeste Homolog 2 Protein - genetics
/ Enhancer of Zeste Homolog 2 Protein - metabolism
/ Epigenesis, Genetic
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - metabolism
/ Extracellular Vesicles - metabolism
/ Gastrointestinal Microbiome
/ Hemolysin Proteins - metabolism
/ Histones - metabolism
/ Humans
/ Medical and Health Sciences
/ Medicin och hälsovetenskap
/ Medicinska och farmaceutiska grundvetenskaper
/ Microbiology in the Medical Area
/ MicroRNAs - metabolism
/ Mikrobiologi inom det medicinska området
/ non-pathogenic Escherichia coli
/ Original
/ outer membrane vesicles
/ pore-forming protein cytolysin A
/ Receptors, CXCR4 - metabolism
/ Signal Transduction
/ STAT3 Transcription Factor - metabolism
/ Tumor Suppressor Protein p53 - metabolism
2025
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Sublytic Activity of a Pore‐Forming Protein From Commensal Bacteria Causes Epigenetic Modulation of Tumour‐Affiliated Protein Expression
Journal Article
Sublytic Activity of a Pore‐Forming Protein From Commensal Bacteria Causes Epigenetic Modulation of Tumour‐Affiliated Protein Expression
2025
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Overview
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. The graphical illustrates how OMVs containing sublytic amounts of ClyA from non‐pathogenic E. coli are internalised into colon cancer cells, causing downregulation of critical cancer‐associated epigenetic signalling pathways and elevated level of the tumour suppressor protein p53.
Publisher
John Wiley and Sons Inc,Wiley
Subject
/ Colonic Neoplasms - genetics
/ Colonic Neoplasms - metabolism
/ Enhancer of Zeste Homolog 2 Protein - genetics
/ Enhancer of Zeste Homolog 2 Protein - metabolism
/ Escherichia coli - metabolism
/ Escherichia coli Proteins - metabolism
/ Extracellular Vesicles - metabolism
/ Hemolysin Proteins - metabolism
/ Humans
/ Medicinska och farmaceutiska grundvetenskaper
/ Microbiology in the Medical Area
/ Mikrobiologi inom det medicinska området
/ non-pathogenic Escherichia coli
/ Original
/ pore-forming protein cytolysin A
/ Receptors, CXCR4 - metabolism
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