Pathogen-selective killing by guanylate-binding proteins as a molecular mechanism leading to inflammasome signaling

• DOI: 10.1038/s41467-022-32127-0
• Publication Date: 2022-07-29T06:04:37Z
• Authors: Shouya Feng; Daniel Enosi Tuip...; Abhimanu Pandey; Weidong Jing; Cheng Shen; Chinh Ngo; Melkamu B. Tessema; Fei-Ju Li; Daniel Fox; Anukriti Mathur; Anyang Zhao; Runli Wang; Klaus Pfeffer; Daniel Degrandi; Masahiro Yamamoto; Patrick C. Reading; Gaetan Burgio; Si Ming Man
• Keywords: Mammals; 0303 health sciences; Bacteria; Inflammasomes; Science; Q; Article; Immunity, Innate; Mice; 03 medical and health sciences; Cytosol; GTP-Binding Proteins; Animals; Carrier Proteins; Signal Transduction

Inflammasomes are cytosolic signaling complexes capable of sensing microbial ligands to trigger inflammation and cell death responses. Here, we show that guanylate-binding proteins (GBPs) mediate pathogen-selective inflammasome activation. We mouse GBP1 GBP3 specifically required for activation during infection with the bacterium Francisella novicida. selectivity derives from a region within N-terminal domain containing charged hydrophobic amino acids, which binds facilitates direct killing F. novicida Neisseria meningitidis, but not other bacteria or mammalian cells. This recognition by this leads pathogen membrane rupture release intracellular content sensing. Our results imply GBPs discriminate between pathogens, confer innate immunity, provide host-inspired roadmap design synthetic antimicrobial peptides may be use against emerging re-emerging pathogens.