Isolation and molecular identification of nematode surface mutants with resistance to bacterial pathogens.

Numerous mutants of the nematode Caenorhabditis elegans with surface abnormalities have been isolated by utilizing their resistance to a variety of bacterial pathogens (Microbacterium nematophilum, Yersinia pseudotuberculosis, and 2 Leucobacter strains), all of which are able to cause disease or death when worms are grown on bacterial lawns containing these pathogens. Previous work led to the identification of 9 srf or bus genes; here, we report molecular identification and characterization of a further 10 surface-affecting genes. Three of these were found to encode factors implicated in glycosylation (srf-2, bus-5, and bus-22), like several of those previously reported; srf-2 belongs to the GT92 family of putative galactosyltransferases, and bus-5 is homologous to human dTDP-D-glucose 4,6-dehydratase, which is implicated in Catel-Manzke syndrome.

Functional analysis of the C. elegans cyld-1 gene reveals extensive similarity with its human homolog.

The human cylindromatosis tumor suppressor (HsCyld) has attracted extensive attention due to its association with the development of multiple types of cancer. HsCyld encodes a deubiquitinating enzyme (HsCYLD) with a broad range of functions that include the regulation of several cell growth, differentiation and death pathways. HsCyld is an evolutionarily conserved gene.

The Invertebrate Lysozyme Effector ILYS-3 Is Systemically Activated in Response to Danger Signals and Confers Antimicrobial Protection in C. elegans.

Little is known about the relative contributions and importance of antibacterial effectors in the nematode C. elegans, despite extensive work on the innate immune responses in this organism. We report an investigation of the expression, function and regulation of the six ilys (invertebrate-type lysozyme) genes of C.

Worm-stars and half-worms: Novel dangers and novel defense.

In a recent paper, we reported the isolation and surprising effects of two new bacterial pathogens for Caenorhabditis and related nematodes. These two pathogens belong to the genus Leucobacter and were discovered co-infecting a wild isolate of Caenorhabditis that had been collected in Cape Verde. The interactions of these bacteria with C.

Two Leucobacter strains exert complementary virulence on Caenorhabditis including death by worm-star formation.

The nematode Caenorhabditis elegans has been much studied as a host for microbial infection. Some pathogens can infect its intestine, while others attack via its external surface. Cultures of Caenorhabditis isolated from natural environments have yielded new nematode pathogens, such as microsporidia and viruses.

Glycosylation genes expressed in seam cells determine complex surface properties and bacterial adhesion to the cuticle of Caenorhabditis elegans.

The surface of the nematode Caenorhabditis elegans is poorly understood but critical for its interactions with the environment and with pathogens. We show here that six genes (bus-2, bus-4, and bus-12, together with the previously cloned srf-3, bus-8, and bus-17) encode proteins predicted to act in surface glycosylation, thereby affecting disease susceptibility, locomotory competence, and sexual recognition. Mutations in all six genes cause resistance to the bacterial pathogen Microbacterium nematophilum, and most of these mutations also affect bacterial adhesion and biofilm formation by Yersinia species, demonstrating that both infection and biofilm formation depend on interaction with complex surface carbohydrates.

The Caenorhabditis elegans bus-2 mutant reveals a new class of O-glycans affecting bacterial resistance.

Microbacterium nematophilum causes a deleterious infection of the C. elegans hindgut initiated by adhesion to rectal and anal cuticle. C.

Signal transduction pathways that function in both development and innate immunity.

C. elegans is developing in importance as a model for innate immunity. Several signaling pathways are known to be required for immune responses to a diverse range of pathogens, including the insulin signaling, p38 MAP kinase and transforming growth factor-beta pathways.

The acyltransferase gene bus-1 exhibits conserved and specific expression in nematode rectal cells and reveals pathogen-induced cell swelling.

Susceptibility to the rectal pathogen Microbacterium nematophilum provides a means of examining hindgut differentiation in C. elegans. Mutants of bus-1 are resistant to infection with this pathogen.

The C. elegans glycosyltransferase BUS-8 has two distinct and essential roles in epidermal morphogenesis.

Ventral enclosure in Caenorhabditis elegans involves migration of epidermal cells over a neuroblast substrate and subsequent adhesion at the ventral midline. Organisation of the neuroblast layer by ephrins and their receptors is essential for this migration. We show that bus-8, which encodes a predicted glycosyltransferase, is essential for embryonic enclosure and acts in or with ephrin signalling to mediate neuroblast organisation and to permit epidermal migration.

Multiple genes affect sensitivity of Caenorhabditis elegans to the bacterial pathogen Microbacterium nematophilum.

Interactions with bacteria play a major role in immune responses, ecology, and evolution of all animals, but they have been neglected until recently in the case of C. elegans. We report a genetic investigation of the interaction of C.

Caenorhabditis elegans as a model for innate immunity to pathogens.

The amenability of the nematode Caenorhabditis elegans for genetic analysis and other experimentation provides a powerful tool for studying host-pathogen interactions. Our current understanding of how C. elegans responds to pathogen challenges is in its infancy, but the discovery that the worm has inducible defence responses, which to some extent parallel those of other organisms, demonstrates the potential of this model organism for the study of innate immunity.

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.