The peptidolytic capacity of the spirochete system

Mäkinen, Kauko K.; Mäkinen, Pirkko‐Liisa

doi:10.1007/s004300050008

Cited by 29 publications

(29 citation statements)

References 32 publications

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“…Proteinases and peptidases may aid in degradation of host tissue and bacterial components to fulfill nutritional requirements, and may contribute to cytotoxicity of periodontal infections (33)(34)(35). Over 25 assorted peptidases, hydrolases, and other putative degradative enzymes were identified in the genome.…”

Section: Resultsmentioning

confidence: 99%

Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes

Seshadri

Myers

Tettelin

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

253

314

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We present the complete 2,843,201-bp genome sequence of Treponema denticola (ATCC 35405) an oral spirochete associated with periodontal disease. Analysis of the T. denticola genome reveals factors mediating coaggregation, cell signaling, stress protection, and other competitive and cooperative measures, consistent with its pathogenic nature and lifestyle within the mixed-species environment of subgingival dental plaque. Comparisons with previously sequenced spirochete genomes revealed specific factors contributing to differences and similarities in spirochete physiology as well as pathogenic potential. The T. denticola genome is considerably larger in size than the genome of the related syphiliscausing spirochete Treponema pallidum. The differences in gene content appear to be attributable to a combination of three phenomena: genome reduction, lineage-specific expansions, and horizontal gene transfer. Genes lost due to reductive evolution appear to be largely involved in metabolism and transport, whereas some of the genes that have arisen due to lineage-specific expansions are implicated in various pathogenic interactions, and genes acquired via horizontal gene transfer are largely phagerelated or of unknown function.

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Section: Resultsmentioning

confidence: 99%

Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes

Seshadri

Myers

Tettelin

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

253

314

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“…The T. denticola genome project under way at The Institute of Genome Research will be a major contribution to the knowledge base. Using these resources and peptide sequences derived from a surface-associated BANAhydrolyzing oligopeptidase of T. denticola (22,23), we demonstrate here that a single conserved gene encodes T. denticola trypsin-like enzyme activity.…”

mentioning

confidence: 94%

“…A BANA-hydrolyzing peptidase of T. denticola has been isolated, and its biochemical activity has been characterized (21,23,25). The activity profile of the outer membrane-associated enzyme showed it to be an oligopeptidase capable of hydrolyzing ester, amide, and peptide bonds involving the carboxyl group arginine and lysine and, combined with partial peptide sequences (22), suggested that it belongs to the superfamily of prolyl oligopeptidases that includes Escherichia coli oligopeptidase B (EC 3.4.21.83). Various forms of the arginine-specific (Rgp) and lysine-specific (Kgp) proteases of P. gingivalis account for most of its trypsin-like activity in vitro (30).…”

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confidence: 99%

The opdB Locus Encodes the Trypsin-Like Peptidase Activity of Treponema denticola

et al. 2001

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High levels of Treponema denticola in subgingival dental plaque are associated with severe periodontal disease. T. denticola, along with Porphyromonas gingivalis and Bacteroides forsythus, are the only cultivatable oral microorganisms that produce significant amounts of "trypsin-like" peptidase activity. The ability of subgingival plaque to hydrolyze N-␣-benzoyl-DL-arginine-2-naphthylamide (BANA) is associated with high levels of one or more of these organisms. The purpose of this study was to identify the gene encoding trypsin-like activity in T. denticola and thus facilitate molecular-level studies of its potential role in disease. Using published peptide sequences of a T. denticola surface-associated oligopeptidase with BANA-hydrolyzing activity, we identified the gene, designated opdB, in an apparently noncoding region of the T. denticola genome unannotated contigs (11/2000; http://www.tigr.org). The opdB gene begins with a TTG start codon and encodes a 685-residue peptide with high homology to the oligopeptidase B family in prokaryotes and eukaryotes. An isogenic T. denticola opdB mutant was constructed by allelic replacement mutagenesis using an ermF/AM gene cassette. The mutant lacked BANA-hydrolyzing activity and had a slightly slower growth rate than the parent strain. This mutant will be used in future studies of interactions of T. denticola with host cells and tissue.

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“…Treponema denticola, Porphyromonas gingivalis, and Tannerella forsythia are strongly associated with periodontal diseases (70). These microorganisms, characterized by their high proteolytic and peptidolytic capacities (35,42,47), can hydrolyze the oral HDPs and inactivate their antimicrobial activity (17,42,60). Nevertheless, these bacteria show different susceptibilities to oral HDPs.…”

mentioning

confidence: 99%

“…These include motility, the ability to attach to host tissues (21), coaggregation with other oral bacteria (41,62), complement evasion mechanisms (53), and the presence of several outer sheath and periplasmic proteolytic and peptidolytic activities (47,63,64). The proteolytic capacity of T. denticola sustains its nutritional requirements (69) and ATP production (65,68).…”

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confidence: 99%

The Antibacterial Activity of LL-37 against Treponema denticola Is Dentilisin Protease Independent and Facilitated by the Major Outer Sheath Protein Virulence Factor

2012

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Host defense peptides are innate immune effectors that possess both bactericidal activities and immunomodulatory functions. Deficiency in the human host defense peptide LL-37 has previously been correlated with severe periodontal disease. Treponema denticola is an oral anaerobic spirochete closely associated with the pathogenesis of periodontal disease. The T. denticola major surface protein (MSP), involved in adhesion and cytotoxicity, and the dentilisin serine protease are key virulence factors of this organism. In this study, we examined the interactions between LL-37 and T. denticola. The three T. denticola strains tested were susceptible to LL-37. Dentilisin was found to inactivate LL-37 by cleaving it at the Lys, Phe, Gln, and Val residues. However, dentilisin deletion did not increase the susceptibility of T. denticola to LL-37. Furthermore, dentilisin activity was found to be inhibited by human saliva. In contrast, a deficiency of the T. denticola MSP increased resistance to LL-37. The MSP-deficient mutant bound less fluorescently labeled LL-37 than the wild-type strain. MSP demonstrated specific, dose-dependent LL-37 binding. In conclusion, though capable of LL-37 inactivation, dentilisin does not protect T. denticola from LL-37. Rather, the rapid, MSPmediated binding of LL-37 to the treponemal outer sheath precedes cleavage by dentilisin. Moreover, in vivo, saliva inhibits dentilisin, thus preventing LL-37 restriction and ensuring its bactericidal and immunoregulatory activities.

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The peptidolytic capacity of the spirochete system

Cited by 29 publications

References 32 publications

Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes

Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes

The opdB Locus Encodes the Trypsin-Like Peptidase Activity of Treponema denticola

The Antibacterial Activity of LL-37 against Treponema denticola Is Dentilisin Protease Independent and Facilitated by the Major Outer Sheath Protein Virulence Factor

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