Host-derived, pore-forming toxin–like protein and trefoil factor complex protects the host against microbial infection

• DOI: 10.1073/pnas.1321317111
• Publication Date: 2014-04-15T03:58:43Z
• Authors: Yang Xiang; Chao Yan; Xiaolong Guo; Kaifeng Zhou; Sheng’an Li; Qian Gao; Xuan Wang; Feng Zhao; Jie Liu; Wen-Hui Lee; Yun Zhang
• Keywords: Male; Models, Molecular; Pore Forming Cytotoxic Proteins; 0301 basic medicine; Inflammasomes; Protein Conformation; Bacterial Toxins; Interleukin-1beta; Molecular Sequence Data; 7. Clean energy; Endocytosis; Immunity, Innate; 3. Good health; Mice; 03 medical and health sciences; 13. Climate action; Comamonas; Host-Pathogen Interactions; Animals; Amino Acid Sequence; Anura; Gram-Negative Bacterial Infections; Lysosomes; Peptides; Escherichia coli Infections

Significance

Pore-forming toxins are a common type of bacterial toxins and are important bacterial virulence factors. Aerolysin is produced by Aeromonas species. It is interesting that aerolysin-like proteins are also found in vertebrates. However, the physiological roles of these proteins are still unknown. Previously, a βγ-crystallin fused aerolysin-like protein (α-subunit) and trefoil factor (β-subunit) complex, hence named βγ-CAT, was identified in frogs. Here, we found that this complex is inducible by bacterial challenge. The complex was able to protect the host from microbial infection. It oligomerized along the endo-lysosome pathway to trigger lysosome destabilization and led to interleukin-1β maturation and secretion via inflammasome activation. Our present work provides functional evidence for uncovering the physiological roles of vertebrate-derived bacterial pore-forming toxin–like proteins.