Begun J et al. (2007) PLoS Pathog "Staphylococcal biofilm exopolysaccharide protects against Caenorhabditis elegans immune defenses."

Calderwood SB, Sifri CD, Begun J, Mack D, Rohde H, Ausubel FM, Gaiani JM

[PLoS Pathog, 2007]

Staphylococcus epidermidis and Staphylococcus aureus are leading causes of hospital-acquired infections that have become increasingly difficult to treat due to the prevalence of antibiotic resistance in these organisms. The ability of staphylococci to produce biofilm is an important virulence mechanism that allows bacteria both to adhere to living and artificial surfaces and to resist host immune factors and antibiotics. Here, we show that the icaADBC locus, which synthesizes the biofilm-associated polysaccharide intercellular adhesin (PIA) in staphylococci, is required for the formation of a lethal S. epidermidis infection in the intestine of the model nematode Caenorhabditis elegans. Susceptibility to S. epidermidis infection is influenced by mutation of the C. elegans PMK-1 p38 mitogen-activated protein (MAP) kinase or DAF-2 insulin-signaling pathways. Loss of PIA production abrogates nematocidal activity and leads to reduced bacterial accumulation in the C. elegans intestine, while overexpression of the icaADBC locus in S. aureus augments virulence towards nematodes. PIA-producing S. epidermidis has a significant survival advantage over ica-deficient S. epidermidis within the intestinal tract of wild-type C. elegans, but not in immunocompromised nematodes harboring a loss-of-function mutation in the p38 MAP kinase pathway gene sek-1. Moreover, sek-1 and pmk-1 mutants are equally sensitive to wild-type and icaADBC-deficient S. epidermidis. These results suggest that biofilm exopolysaccharide enhances virulence by playing an immunoprotective role during colonization of the C. elegans intestine. These studies demonstrate that C. elegans can serve as a simple animal model for studying host-pathogen interactions involving staphylococcal biofilm exopolysaccharide and suggest that the protective activity of biofilm matrix represents an ancient conserved function for resisting predation.

Begun J et al. (2005) Infect Immun "Staphylococcus aureus virulence factors identified by using a high-throughput Caenorhabditis elegans-killing model."

Goldman S, Ausubel FM, Sifri CD, Calderwood SB, Begun J

[Infect Immun, 2005]

Staphylococcus aureus is an important human pathogen that is also able to kill the model nematode Caenorhabditis elegans. We constructed a 2,950-member Tn917 transposon insertion library in S. aureus strain NCTC 8325. Twenty-one of these insertions exhibited attenuated C. elegans killing, and of these, 12 contained insertions in different genes or chromosomal locations. Ten of these 12 insertions showed attenuated killing phenotypes when transduced into two different S. aureus strains, and 5 of the 10 mutants correspond to genes that have not been previously identified in signature-tagged mutagenesis studies. These latter five mutants were tested in a murine renal abscess model, and one mutant harboring an insertion in nagD exhibited attenuated virulence. Interestingly, Tn917 was shown to have a very strong bias for insertions near the terminus of DNA replication.

Zou Y (2006) Neuron "Navigating the anterior-posterior axis with Wnts."

Zou Y

[Neuron, 2006]

Recent studies have begun to shed light on the molecular guidance cues controlling anterior-posterior axon guidance. Two recent studies in the current issue of Developmental Cell show that Wnts play critical roles in patterning processes and directing neuronal migration in C. elegans. Together with previous findings in vertebrates and flies, these new results establish conserved function of Wnts in A-P guidance.

Lee RYN et al. (2003) Comp Funct Genomics "Building a cell and anatomy ontology of Caenorhabditis elegans."

Lee RYN, Sternberg PW

[Comp Funct Genomics, 2003]

We are endowed with a rich knowledge about Caenorhabditis elegans. Its stereotyped anatomy and development has stimulated research and resulted in the accumulation of cell-based information concerning gene expression, and the role of specific cells in developmental signalling and behavioural circuits. To make the information more accessible to sophisticated queries and automated retrieval systems, WormBase has begun to construct a C. elegans cell and anatomy ontology. Here we present our strategies and progress.

Guarente L et al. (1998) Proc Natl Acad Sci U S A "Aging, life span, and senescence."

Guarente L, Ruvkun GB, Amasino R

[Proc Natl Acad Sci U S A, 1998]

Research in the field of aging recently has entered a new era. Model systems have begun to provide insight into cellular, molecular, and organismal changes that are related intimately to aging. One important approach has been the identification of genes that determine the life span of an organism. The very existence of genes that when mutated can extend life span suggests that one or a few processes may be critical in aging and that a slowing of these processes may slow aging itself.

Leiser SF et al. (2011) Aging Cell "HIF-1 modulates longevity and healthspan in a temperature-dependent manner."

Leiser SF, Kaeberlein M, Begun A

[Aging Cell, 2011]

The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25C but not at 15C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Cox GN et al. (1985) Genetics "Genetic mapping of Caenorhabditis elegans collagen genes using DNA polymorphisms as phenotypic markers."

Kramer JM, Carr SH, Cox GN, Hirsh DI

[Genetics, 1985]

In Caenorhabditis elegans collagens comprise a dispersed family of 40- 150 genes, the majority of which probably code for collagen proteins found in the animal's cuticle. The conserved (Gly-X-Y)n triple helix coding sequence of collagen genes has facilitated the isolation of a large number of C. elegans collagen genes by recombinant DNA methods. We have begun a study of the chromosomal organization of these genes by screening laboratory strains of C. elegans for DNA polymorphisms in the regions surrounding collagen genes. Polymorphisms near seven genes have been identified and have been used as phenotypic markers in genetic crosses to assign the genes to linkage groups II, III, IV, and X. Four genes are shown by multifactor crosses to map to a 2-3 map unit interval between unc-24 and unc-22 on chromosome IV.

Dreyer G et al. (1997) Cad Saude Publica "[Lymphatic filariasis: a potentially eradicable disease]"

Coelho G, Dreyer G

[Cad Saude Publica, 1997]

The recent demonstration that single-dose ivermectin, diethylcarbamazine, or a combination of these drugs can profoundly suppress Wuchereria bancrofti and Brugia malayi microfilaremia for periods of six months to two years has led to renewed hope that transmission can be interrupted and lymphatic filariasis eradicated. Based in part on the availability of these new chemotherapeutic tools, the International Task Force for Disease Eradication recently identified lymphatic filariasis as one of the few diseases that could potentially be eradicated. Thus, control programs based on mass treatment (whether supplemented or not by vector control) have begun to be implemented in some endemic areas. We provide a brief review of available anti-filarial drugs for use in humans, including their tolerance and efficacy.

Leiser SF et al. (2013) J Gerontol A Biol Sci Med Sci "Life-span extension from hypoxia in Caenorhabditis elegans requires both HIF-1 and DAF-16 and is antagonized by SKN-1."

Kaeberlein M, Leiser SF, Fletcher M, Begun A

[J Gerontol A Biol Sci Med Sci, 2013]

Stabilization of the hypoxia-inducible factor (HIF-1) protein extends longevity in Caenorhabditis elegans. However, stabilization of mammalian HIF-1 has been implicated in tumor growth and cancer development. Consequently, for the hypoxic response to benefit mammalian health, we must determine the components of the response that contribute to longevity, and separate them from those that cause harm in mammals. Here, we subject adult worms to low oxygen environments. We find that growth in hypoxia increases longevity in wild-type worms but not in animals lacking HIF-1 or DAF-16. Conversely, hypoxia shortens life span in combination with overexpression of the antioxidant stress response protein SKN-1. When combined with mutations in other longevity pathways or dietary restriction, hypoxia extends life span but to varying extents. Collectively, our results show that hypoxia modulates longevity in a complex manner, likely involving components in addition to HIF-1.

Chisholm AD (2013) Annu Rev Cell Dev Biol "Cytoskeletal dynamics in Caenorhabditis elegans axon regeneration."

Chisholm AD

[Annu Rev Cell Dev Biol, 2013]

Axon regeneration after damage is widespread in the animal kingdom, and the nematode Caenorhabditis elegans has recently emerged as a tractable model in which to study the genetics and cell biology of axon regrowth in vivo. A key early step in axon regrowth is the conversion of part of a mature axon shaft into a growth cone-like structure, involving coordinated alterations in the microtubule, actin, and neurofilament systems. Recent attention has focused on microtubule dynamics as a determinant of axon-regrowth ability in several organisms. Live imaging studies have begun to reveal how the microtubule cytoskeleton is remodeled after axon injury, as well as the regulatory pathways involved. The dual leucine zipper kinase family of mixed-lineage kinases has emerged as a critical sensor of axon damage and plays a key role in regulating microtubule dynamics in the damaged axon.