Schulenburg H et al. (2017) Genetics "The Natural Biotic Environment of Caenorhabditis elegans."

Felix MA, Schulenburg H

[Genetics, 2017]

Organisms evolve in response to their natural environment. Consideration of natural ecological parameters are thus of key importance for our understanding of an organism's biology. Curiously, the natural ecology of the model species Caenorhabditis elegans has long been neglected, even though this nematode has become one of the most intensively studied models in biological research. This lack of interest changed 10 yr ago. Since then, an increasing number of studies have focused on the nematode's natural ecology. Yet many unknowns still remain. Here, we provide an overview of the currently available information on the natural environment of C. elegans We focus on the biotic environment, which is usually less predictable and thus can create high selective constraints that are likely to have had a strong impact on C. elegans evolution. This nematode is particularly abundant in microbe-rich environments, especially rotting plant matter such as decomposing fruits and stems. In this environment, it is part of a complex interaction network, which is particularly shaped by a species-rich microbial community. These microbes can be food, part of a beneficial gut microbiome, parasites and pathogens, and possibly competitors. C. elegans is additionally confronted with predators; it interacts with vector organisms that facilitate dispersal to new habitats, and also with competitors for similar food environments, including competitors from congeneric and also the same species. Full appreciation of this nematode's biology warrants further exploration of its natural environment and subsequent integration of this information into the well-established laboratory-based research approaches.

Schulenburg H et al. (2007) Mol Microbiol "The genetics of pathogen avoidance in Caenorhabditis elegans."

Schulenburg H, Ewbank JJ

[Mol Microbiol, 2007]

Much attention is rightly focused on how microbes cause disease, but they can also affect other aspects of host physiology, including behaviour. Indeed, pathogen avoidance behaviours are seen across animal taxa and are probably of major importance in nature. Here, we review what is known about the molecular genetics underlying pathogen avoidance in the nematode Caenorhabditis elegans. In its natural environment, the soil, this animal feeds on microbes and is continuously exposed to a diverse mix of microorganisms. Nematodes that develop efficient behavioural responses that enhance their attraction to sources of food and avoidance of pathogens will have an evolutionary advantage. C. elegans can specifically detect natural products of bacteria, including surfactants (such as serrawettin) and acylated homoserine lactone autoinducers, and it can learn to avoid pathogenic species. To date, several distinct mechanisms have been shown to be involved in pathogen avoidance. They are based on G protein-like, insulin-like and neuronal serotonin signalling. We discuss recent findings on the mechanisms of pathogen recognition in C. elegans, the relationship between alternative behavioural defences and also between these and other life-history traits. We propose that the selective pressure associated with avoidance behaviours influence both pathogen and host evolution.

Schulenburg H (2018) Curr Biol "Infection Models: Novel Potato Blight-like Pathogens in Worms."

Schulenburg H

[Curr Biol, 2018]

Oomycetes are best known as plant pathogens, causing for example potato blight. Other oomycetes are deadly yet less well studied pathogens of animals including humans. Osman and colleagues now present the nematode C.elegans as a new, genetically tractable host model that should enhance our general understanding of oomycete infections.

Schulenburg H et al. (2004) Parasitology "Natural variation in the response of Caenorhabditis elegans towards Bacillus thuringiensis."

Schulenburg H, Muller S

[Parasitology, 2004]

Almost nothing is known about the natural ecology of the nematode Caenorhabditis elegans, including its interactions with parasites. To help rectify this discrepancy, we assessed natural variation in the response of C. elegans towards a potential parasite, the soil bacterium Bacillus thuringiensis. Our results show that 10 isolates from across the world differ significantly in survival rate and infection level when Confronted with a parasitic strain of B. thuringiensis. Furthermore, behavioural responses are identified as an important component of C. elegans defence, inducing evasion and possibly reduced ingestion of parasites. Again, the natural isolates show significant differences in these traits. In conclusion, worm defence is indicated to be complex and variable across space, implying that parasites play an important role in the ecology, of this species. Based on these results, we expect C. elegans to be a promising model host for future analysis of the evolutionary dynamics of parasite-host interactions.

Schulenburg H et al. (2008) BMC Evol Biol "Diversification and adaptive sequence evolution of Caenorhabditis lysozymes (Nematoda: Rhabditidae)."

Boehnisch C, Schulenburg H

[BMC Evol Biol, 2008]

ABSTRACT: BACKGROUND: Lysozymes are important model enzymes in biomedical research with a ubiquitous taxonomic distribution ranging from phages up to plants and animals. Their main function appears to be defence against pathogens, although some of them have also been implicated in digestion. Whereas most organisms have only few lysozyme genes, nematodes of the genus Caenorhabditis possess a surprisingly large repertoire of up to 15 genes. RESULTS: We used phylogenetic inference and sequence analysis tools to assess the evolution of lysozymes from three congeneric nematode species, Caenorhabditis elegans, C. briggsae, and C. remanei. Their lysozymes fall into three distinct clades, one belonging to the invertebrate-type and the other two to the protist-type lysozymes. Their diversification is characterised by (i) ancestral gene duplications preceding species separation followed by maintenance of genes, (ii) possibly ancestral duplications followed by gene loss in some of the species, and (iii) recent duplications after divergence of species. Both ancestral and recent gene duplications are associated in several cases with signatures of adaptive sequence evolution, indicating that diversifying selection contributed to lysozyme differentiation. Current data strongly suggests that genetic diversity translates into functional diversity. CONCLUSIONS: Gene duplications are a major source of evolutionary innovation. Our analysis provides an evolutionary framework for understanding the diversification of lysozymes through gene duplication and subsequent differentiation. This information is expected to be of major value in future analysis of lysozyme function and in studies of the dynamics of evolution by gene duplication.

Schulenburg H et al. (2004) Immunol Rev "Evolution of the innate immune system: the worm perspective."

Ewbank JJ, Schulenburg H, Kurz CL

[Immunol Rev, 2004]

Simple model organisms that are amenable to comprehensive experimental analysis can be used to elucidate the molecular genetic architecture of complex traits. They can thereby enhance our understanding of these traits in other organisms, including humans. Here, we describe the use of the nematode Caenorhabditis elegans as a tractable model system to study innate immunity. We detail our current understanding of the worm's immune system, which seems to be characterized by four main signaling cascades: a p38 mitogen-activated protein kinase, a transforming growth factor-beta-like, a programed cell death, and an insulin-like receptor pathway. Many details, especially regarding pathogen recognition and immune effectors, are only poorly characterized and clearly warrant further investigation. We additionally speculate on the evolution of the C. elegans immune system, taking into special consideration the relationship between immunity, stress responses and digestion, the diversification of the different parts of the immune system in response to multiple and/or coevolving pathogens, and the trade-off between immunity and host life history traits. Using C. elegans to address these different facets of host-pathogen interactions provides a fresh perspective on our understanding of the structure and complexity of innate immune systems in animals and plants.

Schulenburg H et al. (2004) BMC Evol Biol "Diversity and specificity in the interaction between Caenorhabditis elegans and the pathogen Serratia marcescens."

Ewbank JJ, Schulenburg H

[BMC Evol Biol, 2004]

BACKGROUND: Co-evolutionary arms races between parasites and hosts are considered to be of immense importance in the evolution of living organisms, potentially leading to highly dynamic life-history changes. The outcome of such arms races is in many cases thought to be determined by frequency dependent selection, which relies on genetic variation in host susceptibility and parasite virulence, and also genotype-specific interactions between host and parasite. Empirical evidence for these two prerequisites is scarce, however, especially for invertebrate hosts. We addressed this topic by analysing the interaction between natural isolates of the soil nematode Caenorhabditis elegans and the pathogenic soil bacterium Serratia marcescens. RESULTS: Our analysis reveals the presence of i) significant variation in host susceptibility, ii) significant variation in pathogen virulence, and iii) significant strain- and genotype-specific interactions between the two species. CONCLUSIONS: The results obtained support the previous notion that highly specific interactions between parasites and animal hosts are generally widespread. At least for C. elegans, the high specificity is observed among isolates from the same population, such that it may provide a basis for and/or represent the outcome of co-evolutionary adaptations under natural conditions. Since both C. elegans and S. marcescens permit comprehensive molecular analyses, these two species provide a promising model system for inference of the molecular basis of such highly specific interactions, which are as yet unexplored in invertebrate hosts.

Schulenburg H et al. (2008) Immunobiology "Specificity of the innate immune system and diversity of C-type lectin domain (CTLD) proteins in the nematode Caenorhabditis elegans."

Schulenburg H, Weiner J, Bornberg-Bauer E, Hoeppner MP

[Immunobiology, 2008]

The nematode Caenorhabditis elegans has become an important model for the study of innate immunity. Its immune system is based on several signaling cascades, including a Toll-like receptor, three mitogen-activated protein kinases (MAPK), one transforming growth factor-beta (TGF-beta), the insulin-like receptor (ILR), and the programmed cell death (PCD) pathway. Furthermore, it also involves C-type lectin domain- (CTLD) containing proteins as well as several classes of antimicrobial effectors such as lysozymes. Almost all components of the nematode immune system have homologs in other organisms, including humans, and are therefore likely of ancient evolutionary origin. At the same time, most of them are part of a general stress response, suggesting that they only provide unspecific defense. In the current article, we re-evaluate this suggestion and explore the level of specificity in C. elegans innate immunity, i.e. the nematode''s ability to mount a distinct defense response towards different pathogens. We draw particular attention to the CTLD proteins, which are abundant in the nematode genome (278 genes) and many of which show a pathogen-specific response during infection. Specificity may also be achieved through the differential activation of antimicrobial genes, distinct functions of the immunity signaling cascades as well as signal integration across pathways. Taken together, our evaluation reveals high potential for immune specificity in C. elegans that may enhance the nematode''s ability to fight off pathogens.

Hasshoff M et al. (2007) FASEB J "The role of Caenorhabditis elegans insulin-like signaling in the behavioral avoidance of pathogenic Bacillus thuringiensis."

Hasshoff M, Bohnisch C, Hasert B, Tonn D, Schulenburg H

[FASEB J, 2007]

Pathogens cause damage, and their elimination requires activation of the costly immune response. A highly economic defense strategy should thus be the behavioral avoidance of pathogens, as manifested in humans by all aspects of hygiene or revulsion at pathogen-rich material. Despite its potential importance, behavioral defenses have as yet received only little attention in biomedical research--in stark contrast to the physiological immune system. In the present study, the genetics of such behavioral defenses are elucidated in a simple model organism, the nematode Caenorhabditis elegans. We show for the first time that mutations in the insulin-like receptor (ILR) pathway lead to two distinct behavioral responses against pathogenic strains of the Gram-positive bacterium Bacillus thuringiensis (BT), including the physical evasion of pathogens and their reduced oral uptake. Since this pathway also contributes to nematode stress resistance, the results surprisingly reveal a genetic link between physiological and behavioral defenses. Considering that many signaling pathways have conserved their functions across evolution, including the ILR pathway, this signaling cascade may represent an interesting candidate regulator for behavioral defenses in more complex organisms, including humans.--Hasshoff M., Bohnisch C., Tonn D., Hasert B., Schulenburg H. The role of Caenorhabditis elegans insulin-like signaling in the behavioral avoidance of pathogenic Bacillus thuringiensis.

Thomas JH et al. (1994) Worm Breeder's Gazette "lin-36, a Class B Synthetic Multivulva Gene, Encodes a Novel Protein"

Thomas JH, Horvitz HR

[Worm Breeder's Gazette, 1994]

lin-36, a Class B Synthetic Multivulva Gene, Encodes a Novel Protein Jeffrey H. Thomas and H. Robert Horvitz, HHMI, Dept. Biology, MIT, Cambridge, MA 02139, USA