Dataset Information

Fusobacterium nucleatum outer membrane proteins Fap2 and RadD induce cell death in human lymphocytes.

ABSTRACT: 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 pathogen Fusobacterium 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-free F. 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.

SUBMITTER: Kaplan CW

PROVIDER: S-EPMC2976331 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fusobacterium nucleatum outer membrane proteins Fap2 and RadD induce cell death in human lymphocytes.

Kaplan Christopher W CW Ma Xiaoyuan X Paranjpe Avina A Jewett Anahid A Lux Renate R Kinder-Haake Susan S Shi Wenyuan W

Infection and immunity 20100907 11

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 pathogen Fusobacterium ...[more]

PMID: 20823215

Similar Datasets

Project description:IntroductionMetastasis is an important cause of high mortality and lethality of oral cancer. Fusobacterium nucleatum (Fn) can promote tumour metastasis. Outer membrane vesicles (OMVs) are secreted by Fn. However, the effects of Fn-derived extracellular vesicles on oral cancer metastasis and the underlying mechanisms are unclear.ObjectivesWe aimed to determine whether and how Fn OMVs mediate oral cancer metastasis.MethodsOMVs were isolated from brain heart infusion (BHI) broth supernatant of Fn by ultracentrifugation. Tumour-bearing mice were treated with Fn OMVs to evaluate the effect of OMVs on cancer metastasis. Transwell assays were performed to determine how Fn OMVs affect cancer cell migration and invasion. The differentially expressed genes in Fn OMV-treated/untreated cancer cells were identified by RNA-seq. Transmission electron microscopy, laser confocal microscopy, and lentiviral transduction were used to detect changes in autophagic flux in cancer cells stimulated with Fn OMVs. Western blotting assay was performed to determine changes in EMT-related marker protein levels in cancer cells. Fn OMVs' effects on migration after blocking autophagic flux by autophagy inhibitors were determined by in vitro and in vivo experiments.ResultsFn OMVs were structurally similar to vesicles. In the in vivo experiment, Fn OMVs promoted lung metastasis in tumour-bearing mice, while chloroquine (CHQ, an autophagy inhibitor) treatment reduced the number of pulmonary metastases resulting from the intratumoral Fn OMV injection. Fn OMVs promoted the migration and invasion of cancer cells in vivo, leading to altered expression levels of EMT-related proteins (E-cadherin downregulation; Vimentin/N-cadherin upregulation). RNA-seq showed that Fn OMVs activate intracellular autophagy pathways. Blocking autophagic flux with CHQ reduced in vitro and in vivo migration of cancer cells induced by Fn OMVs as well as reversed changes in EMT-related protein expression.ConclusionFn OMVs not only induced cancer metastasis but also activated autophagic flux. Blocking autophagic flux weakened Fn OMV-stimulated cancer metastasis.

Dataset Information

Fusobacterium nucleatum outer membrane proteins Fap2 and RadD induce cell death in human lymphocytes.

Publications

Fusobacterium nucleatum outer membrane proteins Fap2 and RadD induce cell death in human lymphocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets