Isolation and identification of a cytopathic activity in Tannerella forsythia

Nakajima, Takuma; Tomi, N.; Fukuyo, Yayoi; Ishikura, Hiroaki; Ohno, Yuka; Arvind, Ramanathan; Arai, Takao; Ishikawa, Isao; Arakawa, Shin’ichi

doi:10.1016/j.bbrc.2006.10.012

Cited by 27 publications

(37 citation statements)

References 14 publications

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“…Apart from serine proteinase activity there is also evidence for expression of cysteine proteinase prtH by T. forsythia (34). PrtH has recently been identified to be identical to a protein named forsythia detaching factor (35) and it appears to be related to caspases (36). Beside the above, T. forsythia can probably express and secrete many other peptidases since it harbors genes encoding putative secretory enzymes which have not been functionally studied yet.…”

Section: Discussionmentioning

confidence: 99%

A Metalloproteinase Karilysin Present in the Majority of Tannerella forsythia Isolates Inhibits All Pathways of the Complement System

Jusko

Potempa

Karim

et al. 2012

The Journal of Immunology

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Tannerella forsythia is a poorly studied pathogen despite being one of the main causes of periodontitis, which is an inflammatory disease of the supporting structures of the teeth. We found that despite being recognized by all complement pathways T. forsythia is resistant to killing by human complement, which is present at up to 70% of serum concentration in gingival crevicular fluid. Incubation of human serum with karilysin, a metalloproteinase of T. forsythia, resulted in a decrease in bactericidal activity of the serum. T. forsythia strains expressing karilysin at higher levels were more resistant than low expressing strain. Furthermore, the low expressing strain was significantly more opsonized with C3b and membrane attack complex from serum compared to the other strains. The high expressing strain was more resistant to killing in human blood. The protective effect of karilysin against serum bactericidal activity was attributable to its ability to inhibit complement at several stages. The classical and lectin complement pathways were inhibited due to the efficient degradation of mannose-binding lectin, ficolin-2, ficolin-3 and C4 by karilysin, while inhibition of the terminal pathway was caused by degradation of C5. Interestingly, karilysin was able to release biologically active C5a peptide in human plasma and induce migration of neutrophils. Importantly, we detected the karilysin gene in over 90% of gingival crevicular fluid samples containing T. forsythia obtained from patients with periodontitis. Taken together, the newly characterized karilysin appears to be an important virulence factor of T. forsythia and might have several important implications for immune evasion.

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Section: Discussionmentioning

confidence: 99%

A Metalloproteinase Karilysin Present in the Majority of Tannerella forsythia Isolates Inhibits All Pathways of the Complement System

Jusko

Potempa

Karim

et al. 2012

The Journal of Immunology

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“…The only proteolytic enzyme that has been characterized in detail was PrtH, a cysteine protease of a caspase-like fold. PrtH detaches adherent cells from the substratum and increases IL-8 expression (Nakajima et al, 2006; Pei and Grishin, 2009). Our knowledge has been increased immensely with the discovery of a novel family of six secretory proteases in T. forsythia that includes three serine proteases (mirolase, miropsin-1, and miropsin-2) and three metalloproteases (karilysin, mirolysin, and forsilysin).…”

Section: Introductionmentioning

confidence: 99%

Mirolysin, a LysargiNase from Tannerella forsythia, proteolytically inactivates the human cathelicidin, LL-37

Koneru

Książek

Waligorska

et al. 2016

Biological Chemistry

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Tannerella forsythia is a periodontal pathogen expressing six secretory proteolytic enzymes with a unique multidomain structure referred to as KLIKK proteases. Two of these proteases, karilysin and mirolysin, were previously shown to protect the bacterium against complement-mediated bactericidal activity. The latter metalloprotease, however, was not characterized at the protein level. Therefore, we purified recombinant mirolysin and subjected it to detailed biochemical characterization. Mirolysin was obtained as a 66 kDa zymogen, which autoproteolytically processed itself into a 31 kDa active form via truncations at both the N- and C-termini. Further autodegradation was prevented by calcium. Substrate specificity was determined by the S1’ subsite of the substrate-binding pocket, which shows strong preference for Arg and Lys at the carbonyl side of a scissile peptide bond (P1’ residue). The protease cleaved an array of host proteins, including human fibronectin, fibrinogen, complement proteins C3, C4, and C5, and the antimicrobial peptide, LL-37. Degradation of LL-37 abolished not only the bactericidal activity of the peptide, but also its ability to bind lipopolysaccharide (LPS), thus quenching the endotoxin proinflammatory activity. Taken together, these results indicate that, through cleavage of LL-37 and complement proteins, mirolysin might be involved in evasion of the host immune response.

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“…It is implicated in the development of periodontitis (37), a chronic inflammatory disease resulting in the destruction of connective tissue supporting teeth as well as bone, leading to tooth loss. A number of putative virulence factors have been identified in T. forsythia (33), such as a cell surface-associated leucine-rich-repeat BspA protein (34), a surface S layer (28,30), an ␣-D-glucosidase and an N-acetyl-␤-glucosaminidase (14), proteases (9,29), apoptosis-inducing activity (23), and sialidases (3,22). Sialidases are glycohydrolases which release the terminal sialic acid residues from sialoglycoconjugates.…”

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confidence: 99%

Role of Tannerella forsythia NanH Sialidase in Epithelial Cell Attachment

2011

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Tannerella forsythia is a Gram-negative oral anaerobe which contributes to the development of periodontitis, an inflammatory disease of the tooth-supporting tissues leading to tooth loss. The mechanisms by which this bacterium colonizes the oral cavity are poorly understood. The bacterium has been shown to express two distinct sialidases, namely, SiaHI and NanH, with the latter being the major sialidase. Bacterial sialidases can play roles in pathogenesis by cleaving sialic acids on host glycoproteins, destroying their integrity, and/or unmasking hidden epitopes on host surfaces for colonization. In the present study, we investigated the roles of the SiaHI and NanH sialidases by generating and characterizing specific deletion mutants. Our results showed that the NanH deficiency resulted in a total loss of sialidase activity associated with the outer-membrane and secreted fractions. On the other hand, the SiaHI deficiency resulted in only a slight reduction in the total sialidase activity, with no significant differences in the levels of sialidase activity in the outer membrane or secreted fractions compared to that in the wild-type strain. The results demonstrated that NanH is both surface localized and secreted. The NanH-deficient mutant but not the SiaHI-deficient mutant was significantly attenuated in epithelial cell binding and invasion abilities compared to the wild-type strain. Moreover, the NanH-deficient mutant alone was impaired in cleaving surface sialic acids on epithelial cells. Thus, our study suggests that NanH sialidase might play roles in bacterial colonization by exposing sialic acid-hidden epitopes on epithelial cells.

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Isolation and identification of a cytopathic activity in Tannerella forsythia

Cited by 27 publications

References 14 publications

A Metalloproteinase Karilysin Present in the Majority of Tannerella forsythia Isolates Inhibits All Pathways of the Complement System

A Metalloproteinase Karilysin Present in the Majority of Tannerella forsythia Isolates Inhibits All Pathways of the Complement System

Mirolysin, a LysargiNase from Tannerella forsythia, proteolytically inactivates the human cathelicidin, LL-37

Role of Tannerella forsythia NanH Sialidase in Epithelial Cell Attachment

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