Sublytic Activity of a Pore-Forming Protein From Commensal Bacteria Causes Epigenetic Modulation of Tumour-Affiliated Protein Expression.
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Toh E, Baryalai P, Nadeem A, Aung KM, Myint SL, Zlatkov N, Alidadi H, Zhu S, Mateus A, Raina DB, Ramstedt M, Uhlin BE, Wai SN
J Extracell Vesicles 14 (8) e70149 [2025-08-00; online 2025-08-19]
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.
PubMed 40825567
DOI 10.1002/jev2.70149
Crossref 10.1002/jev2.70149