A Pyranose-2-Phosphate Motif Is Responsible for Both Antibiotic Import and Quorum-Sensing Regulation in Agrobacterium tumefaciens

PLoS Pathog. 2015 Aug 5;11(8):e1005071. doi: 10.1371/journal.ppat.1005071. eCollection 2015 Aug.

Abstract

Periplasmic binding proteins (PBPs) in association with ABC transporters select and import a wide variety of ligands into bacterial cytoplasm. They can also take up toxic molecules, as observed in the case of the phytopathogen Agrobacterium tumefaciens strain C58. This organism contains a PBP called AccA that mediates the import of the antibiotic agrocin 84, as well as the opine agrocinopine A that acts as both a nutrient and a signalling molecule for the dissemination of virulence genes through quorum-sensing. Here, we characterized the binding mode of AccA using purified agrocin 84 and synthetic agrocinopine A by X-ray crystallography at very high resolution and performed affinity measurements. Structural and affinity analyses revealed that AccA recognizes an uncommon and specific motif, a pyranose-2-phosphate moiety which is present in both imported molecules via the L-arabinopyranose moiety in agrocinopine A and the D-glucopyranose moiety in agrocin 84. We hypothesized that AccA is a gateway allowing the import of any compound possessing a pyranose-2-phosphate motif at one end. This was structurally and functionally confirmed by experiments using four synthetic compounds: agrocinopine 3'-O-benzoate, L-arabinose-2-isopropylphosphate, L-arabinose-2-phosphate and D-glucose-2-phosphate. By combining affinity measurements and in vivo assays, we demonstrated that both L-arabinose-2-phosphate and D-glucose-2-phosphate, which are the AccF mediated degradation products of agrocinopine A and agrocin 84 respectively, interact with the master transcriptional regulator AccR and activate the quorum-sensing signal synthesis and Ti plasmid transfer in A. tumefaciens C58. Our findings shed light on the role of agrocinopine and antibiotic agrocin 84 on quorum-sensing regulation in A. tumefaciens and reveal how the PBP AccA acts as vehicle for the importation of both molecules by means of a key-recognition motif. It also opens future possibilities for the rational design of antibiotic and anti-virulence compounds against A. tumefaciens or other pathogens possessing similar PBPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / metabolism*
  • Adenine Nucleotides / chemistry
  • Adenine Nucleotides / metabolism
  • Agrobacterium tumefaciens / metabolism*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Crystallography, X-Ray
  • Molecular Sequence Data
  • Protein Conformation
  • Quorum Sensing / physiology*
  • Sugar Phosphates / metabolism*

Substances

  • ATP-Binding Cassette Transporters
  • AccA protein, Agrobacterium tumefaciens
  • Adenine Nucleotides
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Sugar Phosphates
  • agrocin 84
  • agrocinopine

Grants and funding

DF, AV, MA, YQ and SM were supported by grant ANR-12-BSV8-0003-01/02/03 from Agence National de la Recherche (France) http://www.agence-nationale-recherche.fr/. JR was supported by a National Science Foundation Grant MCB-1158488 http://www.nsf.gov/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.