Cell paper reveals new family of pore-forming toxins from Enterococcus

This article is from the NEJM Journal Watch Review of Pore-Forming Toxins in Enterococcus Species by George Sakoulas, MD Enterococcus β-barrel pore-forming toxins recognize HLA-1 in vitro complex and mediate cytotoxicity
.

Various bacterial pore-forming toxins (PFTs) can mediate toxicity through epithelial cell barrier dysfunction, immune cytotoxicity, and direct tissue damage
.

Structurally, PET consists of alpha helices or beta barrels
.

β-Barrel PFT selectively binds host protein receptors, thereby identifying specific host species and cell-specific targets
.

Xiong and colleagues discovered Epxs, a family of small β-barrel PFTs with known hemolysin homology to E.
faecalis, E.
faecium, and E.
hirae
.

They applied a genome-wide CRISPR-Cas9 screen to identify the human leukocyte antigen class 1 (HLA-1) complex as the receptor for two of these toxins (Epx2 and Epx3)
.

Homologous major histocompatibility complex class 1 (MHC 1) from horse, porcine and bovine (but not murine) have also been identified
.

Induction of MHC 1 expression sensitizes human cells and intestinal organoids to Epx2- and Epx3-mediated cytotoxicity
.

A strain of Enterococcus faecium carrying the Epx2 toxin induces peripheral blood mononuclear cell death and damages intestinal organoids
.

An antibody that neutralizes Epx2 abrogates cytotoxicity caused by Epx-carrying enterococci
.

Review Bacterial PFTs from several species play a key role in the host-pathogen relationship that underlies the pathophysiology of multiple infectious diseases
.

Pore-forming toxins Epx2 and Epx3 appear to be markedly cytotoxic to monocytes and disrupt intestinal epithelial integrity
.

Their specific roles in human disease remain to be determined
.

Reviewed article Xiong X et al.
Emerging enterococcus pore-forming toxins with MHC/HLA-I as receptors.
Cell 2022 Mar 2; [e-pub].
(https://doi.
org/10.
1016/j.
cell.
2022.
02 .
002) NEJM Journal Watch NEJM Journal Watch (NEJM Journal Watch) is published by the NEJM Group, asking internationally renowned doctors to comment on important papers in the medical field, helping doctors understand and apply the latest developments
.

"NEJM Frontiers of Medicine" translates several articles every week, publishes them on the app and official website, and selects 2-3 articles and publishes them on WeChat
.

Copyright Information This article was translated, written or commissioned by the NEJM Frontiers in Medicine, jointly created by Jiahui Medical Research and Education Group (J-Med) and The New England Journal of Medicine (NEJM)
.

The full text of the Chinese translation and the included figures are exclusively authorized by the NEJM Group
.

If you want to reprint, please leave a message or contact nejmqianyan@nejmqianyan.
cn
.

Unauthorized translation is an infringement, and the copyright owner reserves the right to pursue legal responsibility
.