Acetyl-phosphate is not a global regulatory bridge between virulence and central metabolism in Borrelia burgdorferi

Crystal L. Richards, Kevin A. Lawrence, Hua Su, Youyun Yang, X. Yang, Daniel P. Dulebohn, Frank C. Gherardini

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

In B. burgdorferi, the Rrp2-RpoN-RpoS signaling cascade is a distinctive system that coordinates the expression of virulence factors required for successful transition between its arthropod vector and mammalian hosts. Rrp2(BB0763), an RpoN specific response regulator, is essential to activate this regulatory pathway. Previous investigations have attempted to identify the phosphate donor of Rrp2, including the cognate histidine kinase, Hk2(BB0764), non-cognate histidine kinases such as Hk1, CheA1, and CheA2, and small molecular weight P-donors such as carbamoyl-phosphate and acetyl-phosphate (AcP). In a report by Xu et al., exogenous sodium acetate led to increased expression of RpoS and OspC and it was hypothesized this effect was due to increased levels of AcP via the enzyme AckA (BB0622). Genome analyses identified only one pathway that could generate AcP in B. burgdorferi: the acetate/mevalonate pathway that synthesizes the lipid, undecaprenyl phosphate (C55-P, lipid I), which is essential for cell wall biogenesis. To assess the role of AcP in Rrp2-dependent regulation of RpoS and OspC, we used a unique selection strategy to generate mutants that lacked ackA (bb0622: acetate to AcP) or pta (bb0589: AcP to acetyl-CoA). These mutants have an absolute requirement for mevalonate and demonstrate that ackA and pta are required for cell viability. When the ΔackA or Δpta mutant was exposed to conditions (i.e., increased temperature or cell density) that up-regulate the expression of RpoS and OspC, normal induction of those proteins was observed. In addition, adding 20mM acetate or 20mM benzoate to the growth media of B. burgdorferi strain B31 ΔackA induced the expression of RpoS and OspC. These data suggest that AcP (generated by AckA) is not directly involved in modulating the Rrp2-RpoN-RpoS regulatory pathway and that exogenous acetate or benzoate are triggering an acid stress response in B. burgdorferi.

Original languageEnglish (US)
Article numbere0144472
JournalPLoS One
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

Borrelia burgdorferi
Metabolism
Virulence
virulence
phosphates
metabolism
Acetates
Mevalonic Acid
Benzoates
acetates
Histidine
histidine kinase
Phosphotransferases
Arthropod Vectors
benzoates
Cells
Carbamyl Phosphate
mutants
Sodium Acetate
Acetyl Coenzyme A

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Richards, C. L., Lawrence, K. A., Su, H., Yang, Y., Yang, X., Dulebohn, D. P., & Gherardini, F. C. (2015). Acetyl-phosphate is not a global regulatory bridge between virulence and central metabolism in Borrelia burgdorferi. PLoS One, 10(12), [e0144472]. https://doi.org/10.1371/journal.pone.0144472

Acetyl-phosphate is not a global regulatory bridge between virulence and central metabolism in Borrelia burgdorferi. / Richards, Crystal L.; Lawrence, Kevin A.; Su, Hua; Yang, Youyun; Yang, X.; Dulebohn, Daniel P.; Gherardini, Frank C.

In: PLoS One, Vol. 10, No. 12, e0144472, 01.12.2015.

Research output: Contribution to journalArticle

Richards, Crystal L. ; Lawrence, Kevin A. ; Su, Hua ; Yang, Youyun ; Yang, X. ; Dulebohn, Daniel P. ; Gherardini, Frank C. / Acetyl-phosphate is not a global regulatory bridge between virulence and central metabolism in Borrelia burgdorferi. In: PLoS One. 2015 ; Vol. 10, No. 12.
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