<i>Fusobacterium nucleatum</i> Apoptosis-inducing Outer Membrane Protein

Kaplan, Chris W.; Lux, Renate; Huynh, Tri N.; Jewett, Anahid; Shi, Wenyuan; Haake, Susan Kinder

doi:10.1177/154405910508400803

Cited by 45 publications

(43 citation statements)

References 22 publications

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“…2). The previously described Fap2 homolog AimI (22) was associated with a partial decrease in the ability to induce cell death in Jurkat cells. However, since membranes of the corresponding mutant strain induced cell death in Jurkat cells at levels similar to those observed for wild-type membranes, the underlying mechanism is clearly different from that for Fap2 and RadD.…”

Section: Discussionmentioning

confidence: 87%

“…The current F. nucleatum genetic system has not been successful in transforming strain PK1594, requiring us to identify fap2 homologs present in the transformable F. nucleatum strain ATCC 23726 (21,22,24). Our analysis of the F. nucleatum ATCC 23726 genome identified eight Fap2 homologs, all of which belonged to the OMP family of F. nucleatum proteins and had sequence similarities ranging from 39% to 71%.…”

Section: Resultsmentioning

confidence: 99%

“…Our analysis of the F. nucleatum ATCC 23726 genome identified eight Fap2 homologs, all of which belonged to the OMP family of F. nucleatum proteins and had sequence similarities ranging from 39% to 71%. The recently described arginineinhibitable adhesin RadD (21) showed the least similarity to Fap2 of PK1594, 39%, while the previously characterized AimI displayed about 48% homology (22). The protein from strain ATCC 23726 with the highest (71%) similarity to its counterpart in PK1594 was annotated Fap2 (F. nucleatum ATCC 23726 gene Fn1449).…”

Section: Resultsmentioning

confidence: 99%

“…F. nucleatum ATCC 23726 genes NP_603161.1, NP_603291.1, NP_604343.1, NP_602353.1, NP_602381.1, NP_602692.1, NP_602832.1, and NP_602843.1 were inactivated by single homologous recombination as previously described (9,22,23). Briefly, gene fragments were amplified by PCR using appropriate primers and ligated into pHS31 (22) for single gene mutants and pHS19 (9) when constructing double gene mutants. Plasmids were then used to transform E. coli TOP10 cells.…”

Section: Methodsmentioning

confidence: 99%

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Fusobacterium nucleatumOuter Membrane Proteins Fap2 and RadD Induce Cell Death in Human Lymphocytes

Kaplan

Ma²,

Paranjpe³

et al. 2010

Infect Immun

146

140

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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.

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Section: Discussionmentioning

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Fusobacterium nucleatumOuter Membrane Proteins Fap2 and RadD Induce Cell Death in Human Lymphocytes

Kaplan

Ma²,

Paranjpe³

et al. 2010

Infect Immun

146

140

View full text Add to dashboard Cite

show abstract

“…nucleatum is not known to harbor significant virulence factors. However, it is capable of inducing the secretion of proinflammatory cytokines, downregulating host immunity by inhibiting T cells (78), and inducing apoptosis in lymphocytes (79). It also expresses an IgG Fc binding protein (80) and a weak serine protease (81).…”

Section: Figmentioning

confidence: 99%

Fap2 of Fusobacterium nucleatum Is a Galactose-Inhibitable Adhesin Involved in Coaggregation, Cell Adhesion, and Preterm Birth

et al. 2015

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Fusobacterium nucleatum is a common oral anaerobe involved in periodontitis that is known to translocate and cause intrauterine infections. In the oral environment, F. nucleatum adheres to a large diversity of species, facilitating their colonization and creating biological bridges that stabilize the multispecies dental biofilm. Many of these interactions (called coadherences or coaggregations) are galactose sensitive. Galactose-sensitive interactions are also involved in the binding of F. nucleatum to host cells. Hemagglutination of some F. nucleatum strains is also galactose sensitive, suggesting that a single galactose-sensitive adhesin might mediate the interaction of fusobacteria with many partners and targets. In order to identify the fusobacterial galactose-sensitive adhesin, a system for transposon mutagenesis in fusobacteria was created. The mutant library was screened for hemagglutination deficiency, and three clones were isolated. All three clones were found to harbor the transposon in the gene coding for the Fap2 outer membrane autotransporter. The three fap2 mutants failed to show galactose-inhibitable coaggregation with Porphyromonas gingivalis and were defective in cell binding. A fap2 mutant also showed a 2-log reduction in murine placental colonization compared to that of the wild type. Our results suggest that Fap2 is a galactose-sensitive hemagglutinin and adhesin that is likely to play a role in the virulence of fusobacteria.

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Identification and characterization of a novel Fusobacterium nucleatum adhesin involved in physical interaction and biofilm formation with Streptococcus gordonii

Lima¹,

Shi

Lux

2017

MicrobiologyOpen

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To successfully colonize the oral cavity, bacteria must directly or indirectly adhere to available oral surfaces. Fusobacterium nucleatum plays an important role in oral biofilm community development due to its broad adherence abilities, serving as a bridge between members of the oral biofilm that cannot directly bind to each other. In our efforts to characterize the molecular mechanisms utilized by F. nucleatum to physically bind to key members of the oral community, we investigated the involvement of F. nucleatum outer membrane proteins in its ability to bind to the pioneer biofilm colonizer, Streptococcus gordonii. Here, we present evidence that in addition to the previously characterized fusobacterial adhesin RadD, the interaction between F. nucleatum ATCC 23726 and S. gordonii V288 involves a second outer membrane protein, which we named coaggregation mediating protein A (CmpA). We also characterized the role of CmpA in dual‐species biofilm formation with S. gordonii V288, evaluated growth‐phase‐dependent as well as biofilm expression profiles of radD and cmpA, and confirmed an important role for CmpA, especially under biofilm growth conditions. Our findings underscore the complex set of specific interactions involved in physical binding and thus community integration of interacting bacterial species. This complex set of interactions could have critical implications for the formation and maturation of the oral biofilms in vivo, and could provide clues to the mechanism behind the distribution of organisms inside the human oral cavity.

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Fusobacterium nucleatum Apoptosis-inducing Outer Membrane Protein

Cited by 45 publications

References 22 publications

Fusobacterium nucleatumOuter Membrane Proteins Fap2 and RadD Induce Cell Death in Human Lymphocytes

Fusobacterium nucleatumOuter Membrane Proteins Fap2 and RadD Induce Cell Death in Human Lymphocytes

Fap2 of Fusobacterium nucleatum Is a Galactose-Inhibitable Adhesin Involved in Coaggregation, Cell Adhesion, and Preterm Birth

Identification and characterization of a novel Fusobacterium nucleatum adhesin involved in physical interaction and biofilm formation with Streptococcus gordonii

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