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Microb Physiol ; 31(2): 123-134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34107471


Tannerella forsythia is an anaerobic, fusiform Gram-negative oral pathogen strongly associated with periodontitis, a multibacterial inflammatory disease that leads to the destruction of the teeth-supporting tissue, ultimately causing tooth loss. To survive in the oral habitat, T. forsythia depends on cohabiting bacteria for the provision of nutrients. For axenic growth under laboratory conditions, it specifically relies on the external supply of N-acetylmuramic acid (MurNAc), which is an essential constituent of the peptidoglycan (PGN) of bacterial cell walls. T. forsythia comprises a typical Gram-negative PGN; however, as evidenced by genome sequence analysis, the organism lacks common enzymes required for the de novo synthesis of precursors of PGN, which rationalizes its MurNAc auxotrophy. Only recently insights were obtained into how T. forsythia gains access to MurNAc in its oral habitat, enabling synthesis of the own PGN cell wall. This report summarizes T. forsythia's strategies to survive in the oral habitat by means of PGN salvage pathways, including recovery of exogenous MurNAc and PGN-derived fragments but also polymeric PGN, which are all derived from cohabiting bacteria either via cell wall turnover or decay of cells. Salvage of polymeric PGN presumably requires the removal of peptides from PGN by an unknown amidase, concomitantly with the translocation of the polymer across the outer membrane. Two recently identified exo-lytic N-acetylmuramidases (Tf_NamZ1 and Tf_NamZ2) specifically cleave the peptide-free, exogenous (nutrition source) PGN in the periplasm and release the MurNAc and disaccharide substrates for the transporters Tf_MurT and Tf_AmpG, respectively, whereas the peptide-containing, endogenous (the self-cell wall) PGN stays unattached. This review also outlines how T. forsythia synthesises the PGN precursors UDP-MurNAc and UDP-N-acetylglucosamine (UDP-GlcNAc), involving homologs of the Pseudomonas sp. recycling enzymes AmgK/MurU and a monofunctional uridylyl transferase (named Tf_GlmU*), respectively.

Microbiota , Peptidoglicano , Parede Celular , Tannerella , Tannerella forsythia
Quintessence Int ; 52(1): 20-29, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32696031


Objective: Considering the etiopathogenesis of periodontitis, it is relevant to evaluate the efficacy of the adjunctive use of systemic antimicrobials based on microbial occurrence. This report explores whether patients harboring Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), or Tannerella forsythia (Tf) at baseline could receive greater clinical benefits from adjunctive moxifloxacin (MXF) and amoxicillin plus metronidazole (AM+MT) in comparison to patients without the presence of these microorganisms before therapy for generalized periodontitis. A control group was established that received subgingival debridement (SD) alone.
Method and materials: Thirty-six patients younger than 30 years of age were randomly allocated to one of three treatment groups: SD plus placebo, systemic MXF with SD, or AM+MT combined with SD. Subgingival samples were studied. The effects of the therapies on probing depth and clinical attachment level, including interactions with Aa, Pg, or Tf at baseline, were explored using regression models.
Results: At 6 months, all treatment groups showed improved clinical outcomes in patients harboring Aa, Pg, or Tf at baseline compared to the patients who did not harbor these microorganisms at baseline. Indeed, in the presence of Aa, Pg, or Tf at baseline, the patients receiving antimicrobial protocols showed the most significant gains compared to the control group. Furthermore, the percentage of sites ≥ 6 mm was reduced in the test groups, compared to the control group; these periodontopathogens were not present in sites with probing depth ≥ 6 mm in the MXF group. The interactions of Aa, Pg, and Tf with the test groups significantly improved clinical parameters at 6 months (P < .001). Interestingly, the R2 value in the models that explored clinical attachment gain produced a high degree of correlation (> 0.75), indicating that a high percentage (> 75%) of the total variation in clinical attachment level gain can be explained by the independent variables.
Conclusions: Although all patients benefited from the treatments, patients harboring Aa, Pg, or Tf at baseline showed improved clinical benefits at 6 months, suggesting that Aa, Pg, or Tf at baseline may change the effects of systemic MXF and AM+MT in generalized periodontitis. After 6 months, Aa, Pg, and Tf were not present in sites with probing depth ≥ 6 mm in the MXF group.


Antibacterianos , Metronidazol , Periodontite , Adulto , Aggregatibacter actinomycetemcomitans , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Humanos , Metronidazol/uso terapêutico , Moxifloxacina , Perda da Inserção Periodontal/tratamento farmacológico , Bolsa Periodontal/tratamento farmacológico , Periodontite/tratamento farmacológico , Porphyromonas gingivalis , Tannerella , Tannerella forsythia
Glycobiology ; 30(11): 923-934, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-32337602


Endo-ß-N-acetylglucosaminidases are enzymes that hydrolyze the N,N'-diacetylchitobiose unit of N-glycans. Many endo-ß-N-acetylglucosaminidases also exhibit transglycosylation activity, which corresponds to the reverse of the hydrolysis reaction. Because of these activities, some of these enzymes have recently been used as powerful tools for glycan remodeling of glycoproteins. Although many endo-ß-N-acetylglucosaminidases have been identified and characterized to date, there are few enzymes that exhibit hydrolysis activity toward multibranched (tetra-antennary or more) complex-type N-glycans on glycoproteins. Therefore, we searched for novel endo-ß-N-acetylglucosaminidases that exhibit hydrolysis activity toward multibranched complex-type N-glycans in this study. From database searches, we selected three candidate enzymes from Tannerella species-Endo-Tsp1006, Endo-Tsp1263 and Endo-Tsp1457-and prepared them as recombinant proteins. We analyzed the hydrolysis activity of these enzymes toward N-glycans on glycoproteins and found that Endo-Tsp1006 and Endo-Tsp1263 exhibited hydrolysis activity toward complex-type N-glycans, including multibranched N-glycans, preferentially, whereas Endo-Tsp1457 exhibited hydrolysis activity toward high-mannose-type N-glycans exclusively. We further analyzed substrate specificities of Endo-Tsp1006 and Endo-Tsp1263 using 18 defined glycopeptides as substrates, each having a different N-glycan structure. We found that Endo-Tsp1006 preferred N-glycans with galactose or α2,6-linked sialic acid residues in their nonreducing ends as substrates, whereas Endo-Tsp1263 preferred N-glycans with N-acetylglucosamine residues in their nonreducing ends as substrates.

Acetilglucosaminidase/metabolismo , Glicoproteínas/metabolismo , Polissacarídeos/metabolismo , Tannerella/enzimologia , Acetilglucosaminidase/química , Glicoproteínas/química , Hidrólise , Polissacarídeos/química , Especificidade da Espécie
J Glob Antimicrob Resist ; 22: 215-218, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32169683


OBJECTIVES: Administration of systemic antimicrobials as an adjunct to mechanical treatment of periodontitis and sites with adverse clinical results leads to improved outcomes. This study aimed to assess the antimicrobial susceptibility of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Tannerella forsythia isolated from periodontitis patients to amoxicillin, metronidazole, azithromycin and moxifloxacin. METHODS: A total of 76 patients diagnosed with generalised periodontitis were included in the study. Subgingival samples were processed by culture. Etest was used to determine susceptibility to amoxicillin, metronidazole, azithromycin and moxifloxacin. RESULTS: A total of 141 isolates from 76 patients were evaluated, including 61 P. gingivalis, 43 T. forsythia and 37 A. actinomycetemcomitans. Etest results showed complete susceptibility of A. actinomycetemcomitans, P. gingivalis and T. forsythia to moxifloxacin. However, the isolates presented reduced susceptibility to the other antimicrobial agents investigated. Of the A. actinomycetemcomitans isolates, 70.3%, 40.5% and 89.2% were resistant to amoxicillin, azithromycin and metronidazole, respectively. The P. gingivalis samples showed relatively similar rates of resistance to amoxicillin (24.6%), azithromycin (21.3%) and metronidazole (24.6%). Similarly, 25.6%, 21.0% and 25.6% of the T. forsythia isolates were resistant to amoxicillin, azithromycin, and metronidazole, respectively. CONCLUSION: These findings show that moxifloxacin may be a promising antimicrobial agent against P. gingivalis, T. forsythia and A. actinomycetemcomitans for the treatment of periodontitis. However, amoxicillin, azithromycin and metronidazole were less effective, especially against A. actinomycetemcomitans in vitro.

Anti-Infecciosos , Periodontite , Aggregatibacter actinomycetemcomitans , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Humanos , Periodontite/tratamento farmacológico , Porphyromonas gingivalis , Tannerella , Tannerella forsythia
Med Hypotheses ; 138: 109575, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32088522


Antibody levels to periodontal pathogens in prediction of cardiovascular disease (CVD) mortality were explored using data from a health survey in Oslo in 2000 (Oslo II-study) with 12 1/2 years follow-up. IgG antibodies to four common periodontal pathogens; Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD) all termed collectively the "red complex", and Aggregatibacter actinomycetemcomitans(AA) were analysed. The study sample consisted of 1172 men drawn from a cohort of 6,530 men who participated in the Oslo II-study, where they provided information on medical and dental history. Of the study sample, 548 men had reported prior myocardial infarction (MI) at baseline whereas the remaining 624 men were randomly drawn from the ostensibly healthy participants for comparative analyses. Dental anamnestic information included tooth extractions and oral infections. An inverse relation was found for trend by the quartile risk level of TF predicting CVD mortality, p-value for trend = 0.017. Comparison of the first to fourth quartile of TF antibodies resulted in hazard ratio (HR) = 1.82, 95% confidence interval 1.12-2.94, p = 0.015, adjusted for age, education, diabetes, daily smoking, and systolic blood pressure. Specificity comparing decile 1 to deciles 2-10 of TF predicting mortality was 92.3%. We found an increased HR by low levels of antibodies to the bacterium T. forsythia predicting CVD mortality in a 12 ½ years follow-up in persons who had experienced an MI but not among non-MI men. This novel finding constitutes a plausible causal link between oral infections and CVD mortality.

Doenças Cardiovasculares , Infarto do Miocárdio , Humanos , Masculino , Estudos Prospectivos , Tannerella , Tannerella forsythia