Loss of srf-3-encoded nucleotide sugar transporter activity in Caenorhabditis elegans alters surface antigenicity and prevents bacterial adherence.
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.
Höflich
Jörg
J
ABI/Molecular Neurogenetics, Ludwig-Maximilians University, 80336 Munich, Germany.
Berninsone
Patricia
P
Göbel
Christine
C
Gravato-Nobre
Maria J
MJ
Libby
Brian J
BJ
Darby
Creg
C
Politz
Samuel M
SM
Hodgkin
Jonathan
J
Hirschberg
Carlos B
CB
Baumeister
Ralf
R
D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion; D001692:Biological Transport; D017173:Caenorhabditis elegans; D050260:Carbohydrate Metabolism; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005091:Exons; D006056:Golgi Apparatus / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007438:Introns; D008164:Luminescent Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012276:Ricin / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014531:Uridine Diphosphate Galactose / Q000378:metabolism; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism; D015011:Yersinia pseudotuberculosis
D018076:DNA, Complementary; D008164:Luminescent Proteins; D026901:Membrane Transport Proteins; C488530:Srf-3 protein, C elegans; D049452:Green Fluorescent Proteins; D014531:Uridine Diphosphate Galactose; D014537:Uridine Diphosphate N-Acetylglucosamine; D012276:Ricin