Loss of srf-3-encoded nucleotide sugar transporter activity in Caenorhabditis elegans alters surface antigenicity and prevents bacterial adherence

J Biol Chem. 2004 Jul 16;279(29):30440-8. doi: 10.1074/jbc.M402429200. Epub 2004 Apr 30.

Abstract

During the establishment of a bacterial infection, the surface molecules of the host organism are of particular importance, since they mediate the first contact with the pathogen. In Caenorhabditis elegans, mutations in the srf-3 locus confer resistance to infection by Microbacterium nematophilum, and they also prevent biofilm formation by Yersinia pseudotuberculosis, a close relative of the bubonic plague agent Yersinia pestis. We cloned srf-3 and found that it encodes a multitransmembrane hydrophobic protein resembling nucleotide sugar transporters of the Golgi apparatus membrane. srf-3 is exclusively expressed in secretory cells, consistent with its proposed function in cuticle/surface modification. We demonstrate that SRF-3 can function as a nucleotide sugar transporter in heterologous in vitro and in vivo systems. UDP-galactose and UDP-N-acetylglucosamine are substrates for SRF-3. We propose that the inability of Yersinia biofilms and M. nematophilum to adhere to the nematode cuticle is due to an altered glycoconjugate surface composition of the srf-3 mutant.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Adhesion*
  • Biological Transport*
  • Caenorhabditis elegans
  • Carbohydrate Metabolism*
  • Cell Membrane / metabolism
  • Cloning, Molecular
  • DNA, Complementary / metabolism
  • Dogs
  • Dose-Response Relationship, Drug
  • Exons
  • Golgi Apparatus / metabolism
  • Green Fluorescent Proteins
  • Introns
  • Luminescent Proteins / metabolism
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / physiology*
  • Microscopy, Fluorescence
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Plasmids / metabolism
  • Protein Structure, Tertiary
  • Ricin / pharmacology
  • Sequence Homology, Amino Acid
  • Transfection
  • Uridine Diphosphate Galactose / metabolism
  • Uridine Diphosphate N-Acetylglucosamine / metabolism
  • Yersinia pseudotuberculosis

Substances

  • DNA, Complementary
  • Luminescent Proteins
  • Membrane Transport Proteins
  • Srf-3 protein, C elegans
  • Green Fluorescent Proteins
  • Uridine Diphosphate Galactose
  • Uridine Diphosphate N-Acetylglucosamine
  • Ricin