2023-05-23 パデュー大学
◆Dongqi Liuとその共同研究者たちは、内在性の粘着性タンパク質である内因性Bを使用してLAPを細菌の表面に固定することがリステリアによる感染のために必要であることを明らかにしました。これにより、リステリアに関するより良い理解が可能となり、より効果的な予防策が開発される可能性があります。
◆新たな発見は、特に妊婦を含む感受性のある人々におけるリステリア感染症の予防のための抗体補充やワクチンの開発に役立つ可能性があります。
<関連情報>
- https://www.purdue.edu/newsroom/releases/2023/Q2/laboratory-fishing-expedition-reels-in-a-big-catch-hidden-pathogenic-role-of-a-housekeeping-enzyme-in-listeria.html
- https://www.cell.com/cell-reports/fulltext/S2211-1247(23)00526-0
L. monocytogenesのリステリア接着タンパク質の細胞表面への固定は、病原体形成のためにinternalin Bによって留め置かれる Cell-surface anchoring of Listeria adhesion protein on L. monocytogenes is fastened by internalin B for pathogenesis
Dongqi Liu,Xingjian Bai,Harrison D.B. Helmick,Manalee Samaddar,Mary Anne Roshni Amalaradjou,Xilin Li,Shivendra Tenguria,Nicholas L.F. Gallina,Luping Xu,Rishi Drolia,Uma K. Aryal,Gustavo Marçal Schmidt Garcia Moreira,Michael Hust,Mohamed N. Seleem,Jozef L. Kokini,Raluca Ostafe,Abigail Cox,Arun K. Bhunia
Cell Reports Published:May 11, 2023
DOI:https://doi.org/10.1016/j.celrep.2023.112515
Highlights
•Mass spectrometry identifies InlB as the anchoring partner for secreted LAP
•C-terminal domain of LAP docks InlB GW module via electrostatic forces
•Glu523 and Glu621 in the ADH domain of LAP play a critical role in InlB anchoring
•LAP-InlB complex promotes Lm pathogenesis and systemic spread, including brain
Summary
Listeria adhesion protein (LAP) is a secreted acetaldehyde alcohol dehydrogenase (AdhE) that anchors to an unknown molecule on the Listeria monocytogenes (Lm) surface, which is critical for its intestinal epithelium crossing. In the present work, immunoprecipitation and mass spectrometry identify internalin B (InlB) as the primary ligand of LAP (KD ∼ 42 nM). InlB-deleted and naturally InlB-deficient Lm strains show reduced LAP-InlB interaction and LAP-mediated pathology in the murine intestine and brain invasion. InlB-overexpressing non-pathogenic Listeria innocua also displays LAP-InlB interplay. In silico predictions reveal that a pocket region in the C-terminal domain of tetrameric LAP is the binding site for InlB. LAP variants containing mutations in negatively charged (E523S, E621S) amino acids in the C terminus confirm altered binding conformations and weaker affinity for InlB. InlB transforms the housekeeping enzyme, AdhE (LAP), into a moonlighting pathogenic factor by fastening on the cell surface.
