Abstract
Microsporidia are poorly understood, ubiquitous eukaryotic parasites that are completely dependent on their hosts for replication. With the discovery of microsporidia species naturally infecting the genetically tractable transparent nematode C. elegans, this host has been used to explore multiple areas of microsporidia biology. Here we review results about microsporidia infections in C. elegans, which began with the discovery of the intestinal-infecting species Nematocida parisii. Recent findings include new species identification in the Nematocida genus, with more intestinal-infecting species, and also a species with broader tissue tropism, the epidermal and muscle-infecting species Nematocida displodere. This species has a longer polar tube infection apparatus, which may enable its wider tissue range. After invasion, multiple Nematocida species appear to fuse host cells, which likely promotes their dissemination within host organs. Localized proteomics identified Nematocida proteins that have direct contact with the C. elegans intestinal cytosol and nucleus, and many of these host-exposed proteins belong to expanded, species-specific gene families. On the host side, forward genetic screens have identified regulators of the Intracellular Pathogen Response (IPR), which is a transcriptional response induced by both microsporidia and the Orsay virus, which is also a natural, obligate intracellular pathogen of the C. elegans intestine. The IPR constitutes a novel immune/stress response that promotes resistance against microsporidia, virus, and heat shock. Overall, the Nematocida/C. elegans system has provided insights about strategies for microsporidia pathogenesis, as well as innate defense pathways against these parasites.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bakowski MA et al (2014a) Ubiquitin-mediated response to microsporidia and virus infection in C. elegans. PLoS Pathog 10:e1004200. https://doi.org/10.1371/journal.ppat.1004200
Bakowski MA, Priest M, Young S, Cuomo CA, Troemel ER (2014b) Genome sequence of the microsporidian species Nematocida sp1 strain ERTm6 (ATCC PRA-372). Genome Announc 2:e00905-14. https://doi.org/10.1128/genomeA.00905-14
Balla KM, Andersen EC, Kruglyak L, Troemel ER (2015) A wild C. elegans strain has enhanced epithelial immunity to a natural microsporidian parasite. PLoS Pathog 11:e1004583. https://doi.org/10.1371/journal.ppat.1004583
Balla KM, Luallen RJ, Bakowski MA, Troemel ER (2016) Cell-to-cell spread of microsporidia causes Caenorhabditis elegans organs to form syncytia. Nat Microbiol 1:16144. https://doi.org/10.1038/nmicrobiol.2016.144
Balla KM, Lazetic V, Troemel ER (2019) Natural variation in the roles of C. elegans autophagy components during microsporidia infection. PLoS One 14:e0216011. https://doi.org/10.1371/journal.pone.0216011
Becnel JJ, White SE, Shapiro AM (2005) Review of microsporidia-mosquito relationships: from the simple to the complex. Folia Parasitol (Praha) 52:41–50
Botts MR, Cohen LB, Probert CS, Wu F, Troemel ER (2016) Microsporidia intracellular development relies on myc interaction network transcription factors in the host. G3 (Bethesda) 6:2707–2716. https://doi.org/10.1534/g3.116.029983
Burton NO et al (2021) Intergenerational adaptations to stress are evolutionarily conserved, stress-specific, and have deleterious trade-offs. bioRxiv. https://doi.org/10.1101/2021.05.07.443118
Capella-Gutierrez S, Marcet-Houben M, Gabaldon T (2012) Phylogenomics supports microsporidia as the earliest diverging clade of sequenced fungi. BMC Biol 10:47. https://doi.org/10.1186/1741-7007-10-47
Chen K, Franz CJ, Jiang H, Jiang Y, Wang D (2017) An evolutionarily conserved transcriptional response to viral infection in Caenorhabditis nematodes. BMC Genomics 18:303. https://doi.org/10.1186/s12864-017-3689-3
Corradi N, Pombert JF, Farinelli L, Didier ES, Keeling PJ (2010) The complete sequence of the smallest known nuclear genome from the microsporidian Encephalitozoon intestinalis. Nat Commun 1:77. https://doi.org/10.1038/ncomms1082
Cuomo CA et al (2012) Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth. Genome Res 22:2478–2488. https://doi.org/10.1101/gr.142802.112
Darby C, Cosma CL, Thomas JH, Manoil C (1999) Lethal paralysis of Caenorhabditis elegans by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 96:15202–15207. https://doi.org/10.1073/pnas.96.26.15202
Dimov I, Maduro MF (2019) The C. elegans intestine: organogenesis, digestion, and physiology cell tissue res, p 377:383-396. https://doi.org/10.1007/s00441-019-03036-4
El Jarkass HT, Reinke AW (2020) The ins and outs of host-microsporidia interactions during invasion, proliferation and exit. Cell Microbiol 22:e13247. https://doi.org/10.1111/cmi.13247
El Jarkass HT, Mok C, Schertzberg MR, Fraser AG, Troemel ER, Reinke AW (2022, Jan 7) An intestinally secreted host factor promotes microsporidia invasion of C. elegans. Elife 11:e72458. https://doi.org/10.7554/eLife.72458. Epub ahead of print
Estes KA, Szumowski SC, Troemel ER (2011) Non-lytic, actin-based exit of intracellular parasites from C. elegans intestinal cells. PLoS Pathog 7:e1002227. https://doi.org/10.1371/journal.ppat.1002227
Fasseas MK, Grover M, Drury F, Essmann CL, Kaulich E, Schafer WR, Barkoulas M (2021) Chemosensory Neurons Modulate the Response to Oomycete Recognition in Caenorhabditis elegans Cell Rep 34:108604. https://doi.org/10.1016/j.celrep.2020.108604
Felix MA et al (2011) Natural and experimental infection of Caenorhabditis nematodes by novel viruses related to nodaviruses. PLoS Biol 9:e1000586. https://doi.org/10.1371/journal.pbio.1000586
Haag KL, James TY, Pombert JF, Larsson R, Schaer TM, Refardt D, Ebert D (2014) Evolution of a morphological novelty occurred before genome compaction in a lineage of extreme parasites. Proc Natl Acad Sci U S A 111:15480–15485. https://doi.org/10.1073/pnas.1410442111
Han B, Weiss LM (2017) Microsporidia: obligate intracellular pathogens within the fungal Kingdom. Microbiol Spectr 5:97–113. https://doi.org/10.1128/microbiolspec.FUNK-0018-2016
Keeling PJ, McFadden GI (1998) Origins of microsporidia. Trends Microbiol 6:19–23. https://doi.org/10.1016/S0966-842X(97)01185-2
Kiontke KC, Felix MA, Ailion M, Rockman MV, Braendle C, Penigault JB, Fitch DH (2011) A phylogeny and molecular barcodes for Caenorhabditis, with numerous new species from rotting fruits. BMC Evol Biol 11:339. https://doi.org/10.1186/1471-2148-11-339
Kuo CJ, Hansen M, Troemel E (2018) Autophagy and innate immunity: insights from invertebrate model organisms. Autophagy 14:233–242. https://doi.org/10.1080/15548627.2017.1389824
Lazetic V, Troemel ER (2020) Conservation lost: host-pathogen battles drive diversification and expansion of gene families. FEBS J. https://doi.org/10.1111/febs.15627
Lažetić V, Wu F, Cohen LB et al (2022) The transcription factor ZIP-1 promotes resistance to intracellular infection in Caenorhabditis elegans. Nat Commun 13:17. https://doi.org/10.1038/s41467-021-27621-w
Lee D et al (2021) Balancing selection maintains hyper-divergent haplotypes in Caenorhabditis elegans Nat Ecol Evol 5:794–807. https://doi.org/10.1038/s41559-021-01435-x
Leyva-Diaz E, Stefanakis N, Carrera I, Glenwinkel L, Wang G, Driscoll M, Hobert O (2017) Silencing of repetitive DNA is controlled by a member of an unusual Caenorhabditis elegans gene family. Genetics 207:529–545. https://doi.org/10.1534/genetics.117.300134
Luallen RJ, Reinke AW, Tong L, Botts MR, Felix MA, Troemel ER (2016) Discovery of a natural microsporidian pathogen with a broad tissue tropism in Caenorhabditis elegans. PLoS Pathog 12:e1005724. https://doi.org/10.1371/journal.ppat.1005724
Mahajan-Miklos S, Tan MW, Rahme LG, Ausubel FM (1999) Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans pathogenesis model. Cell 96:47–56. https://doi.org/10.1016/s0092-8674(00)80958-7
Panek J, Gang SS, Reddy KC, Luallen RJ, Fulzele A, Bennett EJ, Troemel ER (2020) A cullin-RING ubiquitin ligase promotes thermotolerance as part of the intracellular pathogen response in Caenorhabditis elegans. Proc Natl Acad Sci U S A 117:7950–7960. https://doi.org/10.1073/pnas.1918417117
Pujol N et al (2001) A reverse genetic analysis of components of the toll signaling pathway in Caenorhabditis elegans. Curr Biol 11:809–821. https://doi.org/10.1016/s0960-9822(01)00241-x
Reddy KC et al (2017) An intracellular pathogen response pathway promotes Proteostasis in C. elegans. Curr Biol 27:3544–3553. https://doi.org/10.1016/j.cub.2017.10.009
Reddy KC et al (2019) Antagonistic paralogs control a switch between growth and pathogen resistance in C. elegans. PLoS Pathog 15:e1007528. https://doi.org/10.1371/journal.ppat.1007528
Reinke AW, Troemel ER (2015) The development of genetic modification techniques in intracellular parasites and potential applications to microsporidia. PLoS Pathog 11:e1005283. https://doi.org/10.1371/journal.ppat.1005283
Reinke AW, Balla KM, Bennett EJ, Troemel ER (2017) Identification of microsporidia host-exposed proteins reveals a repertoire of rapidly evolving proteins. Nat Commun 8:14023. https://doi.org/10.1038/ncomms14023
Schulenburg H, Felix MA (2017) The natural biotic environment of Caenorhabditis elegans. Genetics 206:55–86. https://doi.org/10.1534/genetics.116.195511
Sfarcic I, Bui T, Daniels EC, Troemel ER (2019) Nanoluciferase-based method for detecting gene expression in Caenorhabditis elegans. Genetics 213:1197–1207. https://doi.org/10.1534/genetics.119.302655
Singh J (2021) Harnessing the power of genetics: fast forward genetics in Caenorhabditis elegans. Mol Gen Genomics 296:1–20. https://doi.org/10.1007/s00438-020-01721-6
Sowa JN, Jiang H, Somasundaram L, Tecle E, Xu G, Wang D, Troemel ER (2020) The Caenorhabditis elegans RIG-I homolog DRH-1 mediates the intracellular pathogen response upon viral infection. J Virol 94. https://doi.org/10.1128/JVI.01173-19
Stevens L et al (2019) Comparative genomics of 10 new Caenorhabditis species. Evol Lett 3:217–236. https://doi.org/10.1002/evl3.110
Szumowski SC, Botts MR, Popovich JJ, Smelkinson MG, Troemel ER (2014) The small GTPase RAB-11 directs polarized exocytosis of the intracellular pathogen N. parisii for fecal-oral transmission from C. elegans. Proc Natl Acad Sci U S A 111:8215–8220. https://doi.org/10.1073/pnas.1400696111
Szumowski SC, Estes KA, Popovich JJ, Botts MR, Sek G, Troemel ER (2016) Small GTPases promote actin coat formation on microsporidian pathogens traversing the apical membrane of Caenorhabditis elegans intestinal cells. Cell Microbiol 18:30–45. https://doi.org/10.1111/cmi.12481
Tecle E, Chhan CB, Franklin L, Underwood RS, Hanna-Rose W, Troemel ER (2021) The purine nucleoside phosphorylase pnp-1 regulates epithelial cell resistance to infection in C. elegans. PLoS Pathog 17:e1009350. https://doi.org/10.1371/journal.ppat.1009350
Thompson OA et al (2015) Remarkably divergent regions punctuate the genome assembly of the Caenorhabditis elegans Hawaiian strain CB4856 genetics, p 200:975-989. https://doi.org/10.1534/genetics.115.175950
Troemel ER (2016) Host-microsporidia interactions in caenorhabditis elegans, a model nematode host. Microbiol Spectr 4(5). https://doi.org/10.1128/microbiolspec.FUNK-0003-2016
Troemel ER, Felix MA, Whiteman NK, Barriere A, Ausubel FM (2008) Microsporidia are natural intracellular parasites of the nematode Caenorhabditis elegans. PLoS Biol 6:2736–2752. https://doi.org/10.1371/journal.pbio.0060309
Willis AR, Zhao W, Sukhdeo R, Wadi L, El Jarkass HT, Claycomb JM, Reinke AW (2021) A parental transcriptional response to microsporidia infection induces inherited immunity in offspring. Sci Adv 7(19):eabf3114. https://doi.org/10.1126/sciadv.abf3114
Zhang G, Sachse M, Prevost MC, Luallen RJ, Troemel ER, Felix MA (2016) A large collection of novel nematode-infecting microsporidia and their diverse interactions with Caenorhabditis elegans and other related nematodes. PLoS Pathog 12:e1006093. https://doi.org/10.1371/journal.ppat.1006093
Acknowledgments
Thanks to Michalis Barkoulas, Lakshmi Batachari, Crystal Chhan, Marie-Anne Felix, Vladimir Lazetic, and David Wang for helpful comments on the manuscript.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Ethics declarations
Conflict of Interest
The authors declare that there is no conflict of interest.
Funding
This work was supported by NIH under R01 AG052622, GM114139 to ERT, and NIGMS/NIH award K12GM068524 to ET.
Ethical Approval
The chapter is a review of previously published accounts; as such, no animal or human studies were performed.
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Tecle, E., Troemel, E.R. (2022). Insights from C. elegans into Microsporidia Biology and Host-Pathogen Relationships. In: Weiss, L.M., Reinke, A.W. (eds) Microsporidia. Experientia Supplementum, vol 114. Springer, Cham. https://doi.org/10.1007/978-3-030-93306-7_5
Download citation
DOI: https://doi.org/10.1007/978-3-030-93306-7_5
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-93305-0
Online ISBN: 978-3-030-93306-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)