Sublytic Activity of a Pore‐Forming Protein From Commensal Bacteria Causes Epigenetic Modulation of Tumour‐Affiliated Protein Expression
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,...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-08-01
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| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.70149 |
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| Summary: | 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, 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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| ISSN: | 2001-3078 |