Sublytic activity of a pore-forming protein from commensal bacteria causes epigenetic modulation of tumor-affiliated protein expression

• Cytolysin A (ClyA) is a pore-forming protein expressed at sublytic levels by a strongly silenced gene in non-pathogenic Escherichia coli, including typical commensal isolates in the intestinal microbiome of healthy mammalian hosts. Upon overproduction, the 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 can affect host cells in a profound and remarkable manner. OMVs isolated from ClyA+ E. coli were rapidly internalised into cultured colon cancer cells. The OMV-associated ClyA inhibited the expression of cancer-activating proteins such as H3K27me3, CXCR4, STAT3, and MDM2 via the EZH2/H3K27me3/miR622/CXCR4 signalling axis. Our results demonstrate that sublytic amounts of ClyA in OMVs from non-pathogenic E. coli can target the stability of the EZH2 protein to modulate epigenetics of colon cancer cells 

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Nyckelord

outer membrane vesicles

pore-forming toxin ClyA

cancer cell epigenetics

non-pathogenic E. coli

medicinsk cellbiologi

Medical Cell Biology

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)