Abstract
Cytolysin A (ClyA) is an α-pore forming toxin from pathogenic Escherichia coli (E. coli) and Salmonella enterica. Here, we report that E. coli ClyA assembles into an oligomeric structure in solution in the absence of either bilayer membranes or detergents at physiological temperature. These oligomers can rearrange to create transmembrane pores when in contact with detergents or biological membranes. Intrinsic fluorescence measurements revealed that oligomers adopted an intermediate state found during the transition between monomer and transmembrane pore. These results indicate that the water-soluble oligomer represents a prepore intermediate state. Furthermore, we show that ClyA does not form transmembrane pores on E. coli lipid membranes. Because ClyA is delivered to the target host cell in an oligomeric conformation within outer membrane vesicles (OMVs), our findings suggest ClyA forms a prepore oligomeric structure independently of the lipid membrane within the OMV. The proposed model for ClyA represents a non-classical pathway to attack eukaryotic host cells.
Highlights
Cytolysin A (ClyA) is an ␣-pore-forming toxin secreted from pathogenic E. coli
We show that ClyA does not form transmembrane pores on E. coli lipid membranes
Of ClyA in the Absence of Detergent—It is often observed that Pore-forming toxins (PFTs) monomers assemble to form the oligomeric transmembrane pores upon contacting with detergents or lipid vesicles (30 –32)
Summary
Cytolysin A (ClyA) is an ␣-pore-forming toxin secreted from pathogenic E. coli. Results: ClyA monomer assembles to an oligomeric pre-pore structure independently of lipid membrane and detergent. We report that E. coli ClyA assembles into an oligomeric structure in solution in the absence of either bilayer membranes or detergents at physiological temperature These oligomers can rearrange to create transmembrane pores when in contact with detergents or biological membranes. Because ClyA is delivered to the target host cell in an oligomeric conformation within outer membrane vesicles (OMVs), our findings suggest ClyA forms a prepore oligomeric structure independently of the lipid membrane within the OMV. Pore-forming toxins (PFTs) represent the largest family of bacterial protein toxins and constitute important bacterial virulence factors [1, 2] Their cytolytic function operates by introducing a large, water-filled pore into target cell membranes. Wai et al discovered that ClyA in the OMV adopted a ring-like oligomeric structure when viewed under an electron-microscope [21]
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