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alpha pore-forming toxin (alpha-PFT) hemolysin E (HlyE, ClyA or SheA) in Escherichia coli, Salmonella typhi, and Shigella flexneri, and similar proteins This family of alpha pore-forming toxins (alpha-PFTs) includes hemolysin E (HlyE; also called cytolysin (ClyA) or silent hemolysin A (SheA)), produced by certain strains of Escherichia coli, as well as by Salmonella enterica and Shigella flexneri, among others. HlyE is responsible for the hemolytic activity of certain strains of E. coli, including the pathogenic strain E. coli O157. Distinct from many secreted toxins and effectors, HlyE is delivered by outer-membrane vesicles (OMVs). HlyE is unrelated to the well-characterized pore-forming E. coli hemolysins of the RTX (repeats in toxin) family, hemolysin A (HlyA), and the enterohemolysin encoded by the plasmid borne ehxA gene of E. coli 0157. However, they all have the common structural features of an elongated, entirely alpha-helical domain, except for a short hydrophobic beta-hairpin known as the beta-tongue. The HlyE is monomeric in the periplasm where it forms a disulfide bond to prevent oligomerization. In the OMVs, it oligomerizes via a sequential mechanism to form a circular dodecameric pore structure that is active. The pore structure concentrates the amphipathic helices in the center of the ring-like structure, forming a helical barrel that inserts into the membrane by a wedge-like mechanism. HlyE/ClyA represents a prototype of the structural ClyA family of alpha-PFT which includes toxins that share structural similarity with HlyE, and includes Bacillus cereus HblB, Aeromonas hydrophila AhlB, and Bacillus thuringiensis Cry6Aa. Expression of HlyE in the absence of the RTX toxins is sufficient to give a hemolytic phenotype in E. coli. HlyE is expressed during anaerobic growth of E. coli. Anaerobic expression is controlled by the transcription factor, FNR (regulator of fumarate and nitrate reduction), such that, upon ingestion and entry into the anaerobic mammalian intestine, HlyE is produced and may then contribute to the colonization of the host. |
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