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The nematode genus Strongyloides consists of parasites that live as parthenogenetic females in the small intestines of their vertebrate hosts. In addition to producing parasitic offspring, Strongyloides spp. can also form a facultative free-living generation with males and females. A generalized life cycle of Strongyloides sp. is shown in Figure 1. For a general introduction into the biology of Strongyloides sp. by Mark E. Viney and James B. Lok click here. We work mainly with S. papillosus, a common parasite of sheep and goats, which can be raised in rabbits and with S. ratti, a parasite of rats. We also maintain free living cultures of Parastrongyloides trichosuri, a closely related facultative parasite of Australian possums. Work on P. trichosuri is conduct in collaboration with Warwick Grant from La Trobe University at Melbourne.
Since Strongyloides spp. are not yet established as research models like, for example, the model nematode Caenorhabditis elegans, part of our efforts are dedicated to the developmetn of tools and resources for Strongyloides research. Classical genetic approaches are rarely used with metazoan endo-parasites, largely because the adult stages are usually hidden within hosts, making controlled crosses difficult. The existence of a free-living generation in Strongyloides spp. offers a remarkable opportunity for the experimental manipulation of a parasite. We would like to explore this opportunity and conduct genetic screens in Strongyloides spp. We established a genetic linkage map for S. ratti (in collaboration with Mark Viney, University of Bristol, Nemetschke et al. 2010) and we established a protocol for chemical mutagenesis of S. ratti (Guo et al. 2015). Recently, we devised a protocol for RNAi gene knock down in S. ratti (Dulovic and Streit 2019). We were part of the Strongyloides genome consortium (Hunt et al. 2016) and we followed up the genomic work with transcriptomic (mRNA and small RNA) studies (Baskaran, Jaleta et al. 2017; Jaleta et al. 2017); Holz et al. 2017). We continue to improve the S. papillosus genome assembly and we optimised the methods for single worm genotyping and whole genome sequencing (Zhou et al. 2019).
Strongyloides spp. have intersting life history switches. First, a parthenogentic female (the parasitic female) produces progeny of two sexes (male and female) that differ in their chromosomal make up. Second, female progeny of the parasitic females swich between developing into infective third stage larvae (iL3s) and, upon entry into a host, into adult parasites and becoming free-living sexually reproducing adults. Interstingly the progeny of the free-living generation do not have thes options. They are invariably female and develop into iL3s.
Sex determination and sex chromosomes
The sex determining mechanisms vary within the genus Strongyloides. There are species with true sex chromosomes such that individuals with two X chromosomes (plus two pairs of autosomes) are female and individuals with one X are male. Other species, for example S. papillosus have only two pairs of chromosomes, one of which is considerably larger than the other. Already more tan 30 years ago it was speculated that this is the result of a fusion of the X chromosome with one of the autosomes. In old, cytological studies some authors found no chromosomal differences between the sexes of S. papillosus. Others described that in males a portion of one chromosome is eliminated, thereby creating a hemizygous region (sex specific chromatin diminution). Recently, by combining cytological and molecular genetic approaches, we demonstrated that in S. papillosus males an internal portion of one of the two larger chromosomes is eliminated. Further we showed that the region undergoing chromatin diminution contains a high number of genes and is homologous to the X chromosome of S. ratti. The portions of the longer chromosome that is not diminished corresponds to chromosome number I of S. ratti (Nemetschke et al. 2010). These findings, in combination with comparative studies we performed in collaboration with Warwick Grant (La Trobe University) on the sister taxon Parastrongyloides trichosuri, strongly support the chromosome fusion hypothesis (Kulkarni et al. 2013).
We attempt to understand, how it is achieved that ll larvae produced by the free-living generation are female. So fare we showed that in S. papillosus genetically male determining mature sperm never forms (Nemetschke, 2010; Kulkarni, 2016). Surprisingly, in S. ratti null-X sperm and also some very early embryos with a male karyotype appear do exist but the male embryos may be unviable (Kulkarni, 2016). In order to further investigate how the production of male determinign sperm is avoided, we are conducting a detaild analysis of the spermatgenesis im S. papillosus and S. ratti and for comparison, in Parastrongyloides trichosuri, which does produce male progeny.
The parasitic - free-living switch
This switch is considered to be homologous to the switch between dauer and non-dauer development in some free-living nematodes like C. elegans or Pristionchus pacificus. Using pharmacological and RNAi experiments we could show that, like in C. elegans and P. pacificus, the nuclear hormone receptor DAF-12 is a key player in this switch in Strongyloides spp. in the progeny of the parasitic and of the free-living generations (Ogawa et al. 2009; Dulovic and Streit 2019).
Strongyloidiasis, a human disease caused by mainly Strongyloides stercoralis, is a neglected tropical disease. It is however, not limited to tropical regions. It was long known that human derived S. stercoralis is capable of infecting dogs. However, it is unclear if dogs, and may be other animals, play an important role as a source for S. stercoralis infecting humans. In collaboration with more applied parasitologists we compare S. stercoralis isolated from humans and animals, in particular dogs, using molecular genetic and genomic approaches. Recently we collaborated with the groups of Peter Odermatt at the Swiss Tropical and Publich Health Institute at Basel and with Virak Khieu and Sinuon Muth from the Cambodian National Center for Parasitology, Entomology and Malaria Control at Phnom Penh for work in Cambodia (see Schär, Guo et al. 2014, Jaleta, Zhou et al. 2017) and with the group of Dengyu Liu at the Guangxi Medical University at Nanning, China for a study in the Guangxi province, Southern China. We found that in the wild dogs carry human type S. stercoralis, in addition to at least one presumably dog specific species or subspecies (Jaleta, Zhou et al. 2017). While the S. stercoralis population in humans in Cambodia showed fairly extensive genetic variability (Schär, Guo et al. 2014, Jaleta, Zhou et al. 2017), all S. stercoralis we isolated in Guangxi were phylogenetically closely related with each other and appeared to reproduce predominantly, if not exclusively asexually (Zhou et al. 2019). In collaboration with the group of Atiporn Saeung from the Chiang Mai University we are currently expanding our studies to Thailand.
The filarial nematode Onchocerca ochengi is a parasite of cattle in tropical regions. It is closely related with O. volvulus that causes human onchocerciasis, commonly known as river blindness. The two species of Onchocerca share the insect intermediate host Simulium damnosum. Reproducing adult females of O. ochengi live in nodules in the skin of their host. Males, which are much smaller than the females, are present in the nodules at an average number of about one male per nodule. The young first stage juveniles, called microfilariae, leave the nodule of their mother and wait to be taken up by the intermediate host during a blood meal.
For this project we collaborate closely with Alfons Renz from the University of Tübingen and with the Programme Onchocercoses, a Euro-African research network in Ngoundéré, Cameroon. Recently we initiated a collaboration with the group of Atiporn Saeung from the Chiang Mai University to study Onchocerca spp. in Thailand.
Zhou, S., Fu, X., Pei, P., Kucka, M., Liu, J., Tang, L., Zhan, T., He, S., Chan, Y., Rödelsperger, C., Liu, D. and Streit, A. (2019). Characterization of a non-sexual population of Strongyloides stercoralis with hybrid 18S rDNA haplotypes in Guangxi, Southern China. PLOS Neglected Tropical Diseases,13(5): e0007396. https://doi.org/10.1371/journal.pntd.0007396.
Dulovic, A. and Streit, A. (2019). RNAi-mediated knockdown of daf-12 in the model parasitic nematode Strongyloides ratti. PLOS Pathogens, 15(3): e1007705. https://doi.org/10.1371/journal.ppat.1007705. Step by step protocol.
Jaleta, T. G., Roedelsperger, C., Abanda, B. Eisenbarth, A., Achukwi, M. D, Renz, A. and Streit, A. (2018). Full mitochondrial and nuclear genome comparison confirms that Onchocerca sp. "Siisa" is Onchocerca ochengi. Parasitology Research, 117, 1069-1077.
Holz, A. and Streit, A. (2017). Gain and loss of small RNA classes - characterization of small RNAs in the parasitic nematode family Strongyloididae. Genome Biology and Evolution, 9, 2826-2843. https://doi.org/10.1093/gbe/evx197
Jaleta, T. G., Zhou, S., Bemm, F., Khieu, V., Sinuon, M., Schär, F., Odermatt, P. and Streit, A. (2017). Different but overlapping populations ofStrongyloides stercoralis in dogs and humans - dogs as a possible source for zoonotic strongyloidiasis. PLOS Neglected Tropical Diseases, 11(8): e0005752. https://doi.org/10.1371/journal.pntd.0005752
Jaleta, T., G., Roedelsperger, C. and Streit, A. (2017). Parasitological and transcriptomic comparison of Strongyloides ratti infections in natural and in suboptimal permissive hosts. Experimental Parasitology, 180, 112-118 (special issue "Proceedings of the 27th Meeting of the German Society for Parasitology 2016"). DOI:10.1016/j.exppara.2016.12.003
Streit, A. (2017). Genetics: Modes of Reproduction and Genetic Analysis. Parasitology, 144, 316-326 (special issue on Strongyloides spp.). DOI:10.1017/S0031182016000342
Baskaran, P., Jaleta, T. G., Streit, A. and Rödelsperger, C. (2017). Duplications and positive selection drive the evolution of parasitism-associated gene families in the nematode Strongyloides papillosus. Genome Biology and Evolution, 9, 790-801.
Streit, A. and Davis, R. E. (2016). Chromatin diminution version 2. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net/, DOI: 10.1002/9780470015902.a0001181.pub2 (Review).
Kulkarni, A., Lightfoot, J. W. and Streit, A. (2016). Germline organization in Strongyloides nematodes reveals alternative differentiation and regulation mechanisms. Chromosoma 125, 725-745. doi:10.1007/s00412-015-0562-5
Dulovic, A., Puller, V. and Streit, A. (2016) Optimizing culture conditions for free-living stages of the nematode parasite Strongyloides ratti. Experimental Parasitology 168, 25-30. 10.1016/j.exppara.2016.06.005.
Streit, A., Wang, J., Kang, Y. and Davis, R. E. (2016). Gene Silencing and Sex Determination by Programmed DNA Elimination in Parasitic Nematodes. Current opinion in Microbiology 32 120-127 (Review).
Hunt, V. L., Tsai, I. J., Coghlan, A., Reid, A. J., Holroyd, N., Foth, B. J., Tracey, A., Cotton, J. A., Stanley, E. J., Beasley, H., Bennett, H., Brooks, K., Harsha, B., Kajitani, R., Kulkarni, A., Harbecke, D., Nagayasu, E., Nichol, S., Ogura, Y., Quail, M., Randle, N., Ribeiro, D., Sanchez-Flores, A., Hayashi, T., Itoh, T., Denver, D. R., Grant, W., Stoltzfus, J. D., Lok, J. B., Murayama, H., Wastling, J., Streit, A., Kikuchi, T., Viney, M. E., Matthew Berriman, M. (2016). The Genomic Basis of Parasitism in the Strongyloides Clade of Nematodes. Nature Genetics 48, 299-307. doi:10.1038/ng.3495
Kulkarni, A., Holz, A., Rödelsperger, C., Harbecke, D. and Streit, A. (2016). Differential chromatin amplification and chromosome complements in the germline of Strongyloididae (Nematoda). Chromosoma 125, 125-136. doi:10.1007/s00412-015-0532-y
Guo, L., Chang, Z., Dieterich, C. and Streit, A. (2015). A protocol for chemical mutagenesis in Strongyloides ratti. Experimental Parasitology 158, 2-7 (special issue). .
Witte, H., Moreno, E., Rödelsperger, C., Kim, J. S., Kim, J. S., Streit, A. and Sommer, R. J. (2015). Gene inactivation using the CRISPR/Cas9 system in the nematode Pristionchus pacificus. Development Genes and Evolution 255, 55-62.
Hildebrandt, J. C., Eisenbarth, A., Renz, A. and Streit, A. (2014). Reproductive biology of Onchocerca ochengi, a nodule forming filarial nematode in zebu cattle. Veterinary Parasitology 205, 318-329.
Streit, A. (2014). How to become a parasite without sex chromosomes: a hypothesis for the evolution of Strogyloides sp. and related nematodes. Parasitology 141, 1244-1254 (Review).
Schär, F., Guo. L., Streit, A., Khieu, V., Sinuon, M., Marti, H and Odermatt, P. (2014). Strongyloides stercoralis genotypes in humans in Cambodia. Parasitology Inernational 63, 533-536.
Kulkarni, A., Dyka, A., Nemetschke, L., Grant, W. N. and Streit, A. (2013). Parastrongyloides trichosuri suggests that XX/XO sex determination is ancestral in Strongyloididae (Nematode). Parasitology 140, 1822-1830.
Rödelsperger, C. and Streit, A. (2013). Komplexität im Kleinen - Nematoden-Genome im Vergleich. BIOspektrum 6/13, 606-610 (in German).
Eisenbarth, A., Ekale, D., Hildebrandt, J. C., Achukwi, M. D, Streit, A. and Renz, A. (2013). Molecular evidence of ‘Siisa form’, a new genotype related to Onchocerca ochengi in cattle from North Cameroon. Acta Tropica 127, 261-265.
Rödelsperger, C., Streit, A. and Sommer, R. J. (2012). Structure, function and evolution of the nematode genome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net/ DOI: 10.1002/9780470015902.a0024603 (Review).
Streit, A. (2012) Silencing by throwing away: a role for chromatin diminution. Developmental Cell 23, 918-919 (Preview).
Hildebrandt, J. C., Eisenbarth, A., Renz, A. and Streit, A. (2012). Single worm genotyping demonstrates that Onchocerca ochengi females simultaneously produce progeny sired by different males. Parasitology Research 111, 2217-2221.
Sommer R. J. and Streit, A. (2011). Comparative Genetics and Genomics of Nematodes: Genome Structure, Development and Lifestyle. Annual Review of Genetics 45, 1-20 (Review).
Nemetschke, L., Eberhardt, A. G., Hertzberg, H. and Streit, A. (2010). Genetics, chromatin diminution and sex chromosome evolution in the parasitic nematode genus Strongyloides. Current Biology 20, 1687-1696.
Streit, A. and Sommer, R. J. (2010). Genetics: Random expression goes binary. Nature 463, 891-892 (News and Views).
Nemetschke, L., Eberhardt, A. G., Viney, M. E. and Streit, A. (2010). A genetic map of the animal-parasitic nematode Strongyloides ratti. Molecular and Biochemical Parasitiology 169, 124-127.
Wegewitz, V., Schulenburg, H. and Streit, A. (2009). Do males facilitate the spread of novel phenotypes within populations of the androdioecious nematode Caenorhabditis elegans? Journal of Nematology 41, 247-254.
Minasaki R., Puoti A. and Streit A. (2009). The DEAD-box protein MEL-46 is required in the germ line of the nematode Caenorhabditis elegans. BMC Developmental Biology 9, 35.
Ogawa, A., Streit, A., Antebi, A. and Sommer, R. J. (2009). A conserved endocrine mechanism controls the formation of dauer and infective larvae in nematodes. Current Biology 19, 67-71.
Summary of this article, written for a broad audience (in German). Appeared in the newsletter of the German Society for Parasitology 1/2009.
Eberhardt, A. G., Mayer, W. E., Bonfoh, B. and Streit, A. (2008). The Strongyloides (Nematoda) of sheep and the predominant Strongyloides of cattle form at least two different, genetically isolated populations. Veterinary Parasitology 157, 89-99.
Wegewitz, V., Schulenburg, H. and Streit, A. (2008) Experimental insight into the proximate causes of male persistence variation among two strains of the androdioecious Caenorhabditis elegans (Nematoda). BMC Ecology 8, 12.
Streit, A. (2008). Reproduction in Strongyloides (Nematoda): a life between sex and parthenogenesis. Parasitology 135, 285-294 (Review).
Eberhardt, A. G., Mayer, W. E. and Streit, A. (2007). The free-living generation of the nematode Strongyloides papillosus undergoes sexual reproduction. International Journal for Parasitology 37, 989-1000.
Minasaki, R. and Streit, A. (2007). mel-47, a novel protein required for early cell divisions in the nematode Caenorhabditis elegans. Molecular Genetics and Genomics 277, 315-328.