The Treponema denticola AtcR LytTR domain‐containing response regulator interacts with three architecturally distinct promoter elements: implications for understanding the molecular signaling mechanisms that drive the progression of periodontal disease

Abstract

Treponema denticolais an oral spirochete and periopathogen that transitions from low abundance in healthy subgingival crevices to high abundance in periodontal pockets. The T. denticola response regulator AtcR harbors the relatively rare, LytTR DNA binding domain. LytTR domain containing response regulators control critical transcriptional responses required for environmental adaptation. Using a multi-step bioinformatics approach, 26 strong lytTR recognition motifs were identified in the genome of T. denticola strain 35405. Electrophoretic mobility shift assays (EMSA) demonstrated that AtcR binds to these recogniation motifs. High specificity-high affinity complexes formed with phosphorylated AtcR. The LytTR recognition sequences were found to exist in three distinct promoter architectures designated as LytTR1, LytTR2 and LytTR3 promoters. LytTR1 and LytTR2 promoters harbor σ54 binding sites. The functional diversity of the proteins encoded by the putative AtcR regulon suggests that AtcR sits at the top of a regulatory cascade that plays a central role in facilitating T. denticola’s ability to adapt to changing environmental conditions and thrive in periodontal pockets.

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

“…Ramachandran plotting provided strong support for the predicted AtcR structure as 89.36% of the residues were calculated to have favorable bond angles (Miller et al 2014a). The predicted AtcR structural model suggests that the interaction of AtcR with DNA is also likely to be similar to that of AgrA with strong potential for residues within the loops of AtcR to insert into the major grooves of potential LytTR-DNA motifs.…”

“…While the structure of AtcR has not yet been determined, threading of the AtcR sequence onto the AgrA:DNA complex structure suggests that AtcR and AgrA have similar structures (Miller et al 2014a;Sidote et al 2008). Ramachandran plotting provided strong support for the predicted AtcR structure as 89.36% of the residues were calculated to have favorable bond angles (Miller et al 2014a).…”

“…Most activated RRs regulate gene expression by binding to specific DNA target sequences and influencing transcription. Relative to most bacterial species, T. denticola encodes a limited number of TCR systems (Table 1) and regulators, of which only a few have been partially characterized (Frederick et al 2008Miller et al 2014a;Sarkar et al 2010). T. denticola 35405 encodes 6 HKs, 7RRs, and 2 HK-RR hybrids .…”

“…T. denticola 35405 encodes 6 HKs, 7RRs, and 2 HK-RR hybrids . Among the oral treponemes, the AtcS-AtcR and Hpk2-Rrp2 TCR systems of T. denticola have received the most attention (Frederick et al 2008;Miller et al 2014a;Sarkar et al 2010). The domain organizations for AtcR, AtcS, Rrp2, and Hpk2 are depicted in Fig.…”

“…The accessory role of AgrA in S. aureus, but the potentially essential requirement for AtcR in T. denticola, may simply reflect the greater number of "options" for transcriptional regulation available to S. aureus. As a second approach toward identifying genes potentially regulated by AtcR, Miller et al (2014a) used a bioinformatics approach to search for potential LytTR-DNA recognition motifs. The T. denticola 35405 genome was queried with a consensus LytTR binding recognition motif.…”