Gene Regulation, Two Component Regulatory Systems, and Adaptive Responses in Treponema Denticola

Marconi, Richard T.

doi:10.1007/82_2017_66

Cited by 4 publications

(3 citation statements)

References 104 publications

(132 reference statements)

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“…Because of the low toxicity of AMIX, specificity for anaerobic bacteria and the potential for its accumulation at sites of mucosal inflammation via serum leakage, AMIX may be ideally suited for treatment of PD. The data presented here demonstrate the antimicrobial activity of AMIX against oral treponemes including T. denticola , a keystone periopathogen …”

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confidence: 57%

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Antimicrobial activity of amixicile against Treponema denticola and other oral spirochetes associated with periodontal disease

Reed

O’Bier

Oliver

et al. 2018

Journal of Periodontology

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confidence: 57%

“…The data presented here demonstrate the antimicrobial activity of AMIX against oral treponemes including T. denticola, a keystone periopathogen. 23…”

mentioning

confidence: 99%

Antimicrobial activity of amixicile against Treponema denticola and other oral spirochetes associated with periodontal disease

Reed

O’Bier

Oliver

et al. 2018

Journal of Periodontology

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“…The ensuing tissue damage would create conditions favorable for the growth of T. denticola and other periopathogens. For this reason, T. denticola has been designated as a “keystone pathogen” …”

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confidence: 99%

Plasminogen binding and degradation by Treponema denticola: Identification of the plasminogen binding interface on the FhbB protein

Tegels

Oliver

Miller

et al. 2018

Molecular Oral Microbiology

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Treponema denticola is a proteolytic-anaerobic spirochete whose abundance in the subgingival crevice correlates with periodontal disease severity. Treponema denticola evades serum-mediated killing through the binding of factor H (FH), a negative regulator of the complement system. The T. denticolaFH receptor has been identified as FhbB, an 11.4kDa immunodominant lipoprotein. Three distinct subfamilies of FhbB proteins have been delineated and designated as FhbB1, FhbB2 and FhbB3. In this study we demonstrate that all FhbB variants bind human plasminogen (Plg). Competitive binding analyses revealed that FH and Plg do not compete for binding. Binding studies with FhbB1 site-directed amino acid substitution mutants demonstrated that the interaction domains for FH and Plg on FhbB are separable. Inhibition of Plg-FhbB binding by ε-aminocaproic acid (a lysine analog) indicates that binding is mediated by electrostatic interactions that presumably occur with Lys binding sites contained within Plg "Kringle" domains 1, 2, 4 or 5. Similar to that demonstrated for FH, Plg can also serve as a substrate for the T. denticola protease, dentilisin. The in vivo consequences of dentilisin-mediated cleavage of Plg remained to be determined. The data presented demonstrate that FhbB is a multi-functional protein that may contribute to virulence through several mechanisms including immune evasion, manipulation of the host immune response, adherence or tissue invasion.

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The Treponema denticola PAS Domain-Containing Histidine Kinase Hpk2 Is a Heme Binding Sensor of Oxygen Levels

et al. 2018

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Periodontal disease (PD) results from a shift in the composition of the microbial community of the subgingival crevice. As the bacterial population transitions from Gram-positive bacteria to predominantly Gram-negative anaerobes and spirochetes, dramatic changes occur in the physiological and immunological environment at diseased sites. thrives in periodontal pockets, indicating that it has a unique ability to adapt to changing environmental conditions. Hpk2 (tde1970), a Per-Arnt-Sim motif (PAS) domain-containing histidine kinase (HK), is part of the Hpk2-Rrp2 (tde1969) two-component regulatory (TCR) system. This TCR system is growth phase regulated and has been postulated to play a key role in adaptive responses. In this study, we employ predictive structural analyses and site-directed mutagenesis to investigate the functional role of specific amino acid residues located within the Hpk2 PAS domain. Specific substitutions impacted autophosphorylation (AP), phosphotransfer (PT), oligomerization, and hemin binding. The AP, PT, hemin binding, and oligomerization potential of some mutated Hpk2 proteins differed under aerobic versus anaerobic reaction conditions. The data presented here suggest that the regulatory activity of Hpk2 is linked to diatomic gas levels. In a broader sense, this study highlights the importance of studying proteins produced by anaerobes under conditions that approximate the environment in which they thrive. Periodontal disease affects nearly 60% of the global adult population. Its costs to individuals, and to society as a whole, are enormous. As periodontal disease develops, there is a shift in the composition of the oral microbial community. The bacteria that become dominant are able to cause significant damage to the tissues that support the teeth, leading to tooth loss. is one of the keystone pathogens associated with periodontal disease. An earlier study demonstrated that the Hpk2 and Rrp2 proteins play an important role in adaptive responses. Here, we explore the role of specific Hpk2 amino acids in environmental sensing and function, using structural analyses and site-directed mutagenesis.

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Gene Regulation, Two Component Regulatory Systems, and Adaptive Responses in Treponema Denticola

Cited by 4 publications

References 104 publications

Antimicrobial activity of amixicile against Treponema denticola and other oral spirochetes associated with periodontal disease

Antimicrobial activity of amixicile against Treponema denticola and other oral spirochetes associated with periodontal disease

Plasminogen binding and degradation by Treponema denticola: Identification of the plasminogen binding interface on the FhbB protein

The Treponema denticola PAS Domain-Containing Histidine Kinase Hpk2 Is a Heme Binding Sensor of Oxygen Levels

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