Open AccessFusobacterium nucleatumOuter Membrane Proteins Fap2 and RadD Induce Cell Death in Human Lymphocytes
Author(s) -
Christopher W. Kaplan,
Xiaoyuan Ma,
Avina Paranjpe,
Anahid Jewett,
Renate Lux,
Susan Kinder-Haake,
Wenyuan Shi
Publication year - 2010
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00567-10
Subject(s) - fusobacterium nucleatum , biology , secretion , effector , bacterial outer membrane , jurkat cells , programmed cell death , microbiology and biotechnology , cell , t cell , immunology , apoptosis , biochemistry , bacteria , escherichia coli , immune system , gene , genetics , porphyromonas gingivalis
Bacterially induced cell death in human lymphocytes is an important virulence factor for pathogenic bacteria. Previously discovered mechanisms of bacterially induced cell death are predominantly based on the transfer of bacterial proteins to the target host cell, such as the toxins secreted through type I, II, and VI secretion systems or effector proteins injected through type III, IV, and Vb secretion systems. Here, we report a mechanism employed by the Gram-negative oral pathogenFusobacterium nucleatum for cell death induction of human lymphocytes via two outer membrane proteins (OMPs), Fap2 and RadD, which share regions homologous to autotransporter secretion systems (type Va secretion systems). Genetic and physiological studies established that inactivation of the two OMPs led to significantly reduced ability to trigger cell death in Jurkat cells, while the corresponding double mutant was almost completely attenuated. Additional biochemical and molecular analyses demonstrated that cell-freeF. nucleatum membranes are sufficient to induce cell death in Jurkat cells, suggesting that no active process or effector protein transfer was necessary to induce eukaryotic cell death.