Insight into the Dual Functions of Bacterial Enhancer-Binding Protein Rrp2 of Borrelia burgdorferi

dc.contributor.authorYin, Yanping
dc.contributor.authorYang, Youyun
dc.contributor.authorXiang, Xuwu
dc.contributor.authorWang, Qian
dc.contributor.authorYang, Zhang-Nv
dc.contributor.authorBlevins, Jon
dc.contributor.authorLou, Yongliang
dc.contributor.authorYang, X. Frank
dc.contributor.departmentDepartment of Microbiology & Immunology, IU School of Medicineen_US
dc.date.accessioned2017-08-16T16:55:40Z
dc.date.available2017-08-16T16:55:40Z
dc.date.issued2016-05-15
dc.description.abstractIt is well established that the RpoN-RpoS sigma factor (σ(54)-σ(S)) cascade plays an essential role in differential gene expression during the enzootic cycle of Borrelia burgdorferi, the causative agent of Lyme disease. The RpoN-RpoS pathway is activated by the response regulator/σ(54)-dependent activator (also called bacterial enhancer-binding protein [bEBP]) Rrp2. One unique feature of Rrp2 is that this activator is essential for cell replication, whereas RpoN-RpoS is dispensable for bacterial growth. How Rrp2 controls cell replication, a function that is independent of RpoN-RpoS, remains to be elucidated. In this study, by generating a series of conditional rrp2 mutant strains, we demonstrated that the N-terminal receiver domain of Rrp2 is required for spirochetal growth. Furthermore, a D52A point mutation at the phosphorylation site within the N terminus of Rrp2 abolished cell replication. Mutation of the ATPase motif within the central domain of Rrp2 did not affect spirochetal replication, indicating that phosphorylation-dependent ATPase activity of Rrp2 for σ(54) activation is not required for cell growth. However, deletion of the C-terminal domain or a 16-amino-acid truncation of the helix-turn-helix (HTH) DNA-binding motif within the C-terminal domain of Rrp2 abolished spirochetal replication. It was shown that constitutive expression of rpoS is deleterious to borrelial growth. We showed that the essential nature of Rrp2 is not due to an effect on rpoS These data suggest that phosphorylation-dependent oligomerization and DNA binding of Rrp2 likely function as a repressor, independently of the activation of σ(54), controlling an essential step of cell replication in B. burgdorferi IMPORTANCE: Bacterial enhancer-binding proteins (bEBPs) are a unique group of transcriptional activators specifically required for σ(54)-dependent gene transcription. This work demonstrates that the B. burgdorferi bEBP, Rrp2, has an additional function that is independent of σ(54), that of its essentiality for spirochetal growth, and such a function is dependent on its N-terminal signal domain and C-terminal DNA-binding domain. These findings expand our knowledge on bEBP and provide a foundation to further study the underlying mechanism of this new function of bEBP.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationYin, Y., Yang, Y., Xiang, X., Wang, Q., Yang, Z.-N., Blevins, J., … Yang, X. F. (2016). Insight into the Dual Functions of Bacterial Enhancer-Binding Protein Rrp2 of Borrelia burgdorferi. Journal of Bacteriology, 198(10), 1543–1552. http://doi.org/10.1128/JB.01010-15en_US
dc.identifier.issn1098-5530en_US
dc.identifier.urihttps://hdl.handle.net/1805/13841
dc.language.isoen_USen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.isversionof10.1128/JB.01010-15en_US
dc.relation.journalJournal of Bacteriologyen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectBorrelia burgdorferien_US
dc.subjectgrowth & developmenten_US
dc.subjectDNA Replicationen_US
dc.subjectDNA-Binding Proteinsen_US
dc.subjectgeneticsen_US
dc.subjectmetabolismen_US
dc.titleInsight into the Dual Functions of Bacterial Enhancer-Binding Protein Rrp2 of Borrelia burgdorferien_US
dc.typeArticleen_US
ul.alternative.fulltexthttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859600/en_US
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