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Cell-to-cell spread of microsporidia causes Caenorhabditis elegans organs to form syncytia

Nature Microbiology volume 1, Article number: 16144 (2016) Cite this article

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Abstract

The growth of pathogens is dictated by their interactions with the host environment1. Obligate intracellular pathogens undergo several cellular decisions as they progress through their life cycles inside host cells2. We have studied this process for microsporidian species in the genus Nematocida as they grew and developed inside their co-evolved animal host, Caenorhabditis elegans3–5. We found that microsporidia can restructure multicellular host tissues into a single contiguous multinucleate cell. In particular, we found that all three Nematocida species we studied were able to spread across the cells of C. elegans tissues before forming spores, with two species causing syncytial formation in the intestine and one species causing syncytial formation in the muscle. We also found that the decision to switch from replication to differentiation in Nematocida parisii was altered by the density of infection, suggesting that environmental cues influence the dynamics of the pathogen life cycle. These findings show how microsporidia can maximize the use of host space for growth and that environmental cues in the host can regulate a developmental switch in the pathogen.

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Figure 1: A single N. parisii cell can grow to fill most of the C. elegans intestine.
Figure 2: N. parisii can spread across and fuse host intestinal cells into a syncytial organ.
Figure 3: Spreading across host cells is a conserved microsporidia growth strategy with distinct host cell fusion patterns caused by distantly related Nematocida species.
Figure 4: Nematocida vary in growth and virulence, and the density of infection alters developmental speed.

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References

  1. Gog, J. R. et al. Seven challenges in modeling pathogen dynamics within-host and across scales. Epidemics 10, 45–48 (2015).

    Article  PubMed  Google Scholar 

  2. Casadevall, A. Evolution of intracellular pathogens. Annu. Rev. Microbiol. 62, 19–33 (2008).

    Article  CAS  PubMed  Google Scholar 

  3. Troemel, E. R., Felix, M. A., Whiteman, N. K., Barriere, A. & Ausubel, F. M. Microsporidia are natural intracellular parasites of the nematode Caenorhabditis elegans. PLoS Biol. 6, 2736–2752 (2008).

    Article  CAS  PubMed  Google Scholar 

  4. Cuomo, C. A. et al. Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth. Genome Res. 22, 2478–2488 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Luallen, R. J. et al. Discovery of a natural microsporidian pathogen with a broad tissue tropism in Caenorhabditis elegans. PLoS Pathogens 12, e1005724 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Welch, M. D. & Way, M. Arp2/3-mediated actin-based motility: a tail of pathogen abuse. Cell Host Microbe 14, 242–255 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ciechonska, M. & Duncan, R. Reovirus FAST proteins: virus-encoded cellular fusogens. Trends Microbiol. 22, 715–724 (2014).

    Article  CAS  PubMed  Google Scholar 

  8. French, C. T. et al. Dissection of the Burkholderia intracellular life cycle using a photothermal nanoblade. Proc. Natl Acad. Sci. USA 108, 12095–12100 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nikitas, G. et al. Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin. J. Exp. Med. 208, 2263–2277 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Swann, J., Jamshidi, N., Lewis, N. E. & Winzeler, E. A. Systems analysis of host–parasite interactions. Wiley Interdiscip. Rev. Syst. Biol. Med. 7, 381–400 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Stentiford, G. D. et al. Microsporidia—emergent pathogens in the global food chain. Trends Parasitol. 32, 336–348 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cali, A. & Takvorian, P. M. in Microsporidia: Pathogens of Opportunity (eds Weiss, L. M. & Becnel, J. J. ) 71–133 (Wiley, 2014).

    Google Scholar 

  13. Felix, M. A. & Duveau, F. Population dynamics and habitat sharing of natural populations of Caenorhabditis elegans and C. briggsae. BMC Biol. 10, 59 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bakowski, M. A. et al. Ubiquitin-mediated response to microsporidia and virus infection in C. elegans. PLoS Pathogens 10, e1004200 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Balla, K. M. & Troemel, E. R. Caenorhabditis elegans as a model for intracellular pathogen infection. Cell Microbiol. 15, 1313–1322 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Legouis, R. et al. LET-413 is a basolateral protein required for the assembly of adherens junctions in Caenorhabditis elegans. Nat. Cell Biol. 2, 415–422 (2000).

    Article  CAS  PubMed  Google Scholar 

  17. Sapir, A., Avinoam, O., Podbilewicz, B. & Chernomordik, L. V. Viral and developmental cell fusion mechanisms: conservation and divergence. Dev. Cell 14, 11–21 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Altun, Z. F. & Hall, D. H. Muscle System: Somatic Muscle (WormAtlas, 2009); http://www.wormatlas.org/hermaphrodite/musclesomatic/MusSomaticframeset.html

  19. Altun, Z. F. & Hall, D. H. Epithelial System: Seam Cells (WormAtlas, 2009); http://www.wormatlas.org/hermaphrodite/seam%20cells/Seamframeset.html

  20. Krishna, S., Maduzia, L. L. & Padgett, R. W. Specificity of TGFbeta signaling is conferred by distinct type I receptors and their associated SMAD proteins in Caenorhabditis elegans. Development 126, 251–260 (1999).

    CAS  PubMed  Google Scholar 

  21. Maduzia, L. L. et al. lon-1 regulates Caenorhabditis elegans body size downstream of the dbl-1 TGF beta signaling pathway. Dev. Biol. 246, 418–428 (2002).

    Article  CAS  PubMed  Google Scholar 

  22. Estes, K. A., Szumowski, S. C. & Troemel, E. R. Non-lytic, actin-based exit of intracellular parasites from C. elegans intestinal cells. PLoS Pathogens 7, e1002227 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Szumowski, S. C., Botts, M. R., Popovich, J. J., Smelkinson, M. G. & Troemel, E. R. 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. USA 22, 8215–8220 (2014).

    Article  Google Scholar 

  24. Leitch, G. J., Shaw, A. P., Colden-Stanfield, M., Scanlon, M. & Visvesvara, G. S. Multinucleate host cells induced by Vittaforma corneae (Microsporidia). Folia Parasitol. (Praha) 52, 103–110 (2005).

    Article  Google Scholar 

  25. Morris, D. J., Terry, R. S. & Adams, A. Development and molecular characterisation of the microsporidian Schroedera airthreyi n. sp. in a freshwater bryozoan Plumatella sp. (Bryozoa: Phylactolaemata). J. Eukaryot. Microbiol. 52, 31–37 (2005).

    Article  PubMed  Google Scholar 

  26. Stentiford, G. D. et al. Areospora rohanae n.gen. n.sp. (Microsporidia; Areosporiidae n. fam.) elicits multi-nucleate giant-cell formation in southern king crab (Lithodes santolla). J. Invertebr. Pathol. 118, 1–11 (2014).

    Article  CAS  PubMed  Google Scholar 

  27. Lom, J. & Dykova, I. Microsporidian xenomas in fish seen in wider perspective. Folia Parasitol. (Praha) 52, 69–81 (2005).

    Article  Google Scholar 

  28. Sprague, G. F. Jr & Winans, S. C. Eukaryotes learn how to count: quorum sensing by yeast. Genes Dev. 20, 1045–1049 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Olive, A. J. & Sassetti, C. M. Metabolic crosstalk between host and pathogen: sensing, adapting and competing. Nat. Rev. Microbiol. 14, 221–234 (2016).

    Article  CAS  PubMed  Google Scholar 

  30. Brenner, S. The genetics of Caenorhabditis elegans. Genetics 77, 71–94 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Stiernagle, T. Maintenance of C. elegans (WormBook, 2006); http://www.wormbook.org/chapters/www_strainmaintain/strainmaintain.html

    Book  Google Scholar 

  32. Gurskaya, N. G. et al. Engineering of a monomeric green-to-red photoactivatable fluorescent protein induced by blue light. Nat. Biotechnol. 24, 461–465 (2006).

    Article  CAS  PubMed  Google Scholar 

  33. Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).

    Article  CAS  PubMed  Google Scholar 

  34. Winston, W. M., Molodowitch, C. & Hunter, C. P. Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science 295, 2456–2459 (2002).

    Article  CAS  PubMed  Google Scholar 

  35. Hoch, H. C., Galvani, C. D., Szarowski, D. H. & Turner, J. N. Two new fluorescent dyes applicable for visualization of fungal cell walls. Mycologia 97, 580–588 (2005).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank M. Botts, K. Reddy and A. Reinke for comments on the manuscript. Some C. elegans strains were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health (NIH) Office of Research Infrastructure Programs Grant P40 OD010440. This work was supported by National Science Foundation Graduate Research fellowships to K.M.B. and R.J.L., NIH grant no. R01GM114139, the David and Lucile Packard Foundation and a Burroughs Wellcome Fund fellowship to E.R.T.

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Authors and Affiliations

  1. Division of Biological Sciences, Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA

    Keir M. Balla, Robert J. Luallen, Malina A. Bakowski & Emily R. Troemel

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  2. Robert J. Luallen
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Contributions

K.M.B., R.J.L. and E.R.T. designed the experiments. K.M.B. and R.J.L. performed the experiments and analysed the data. M.A.B. generated the ERT147 transgenic strain. R.J.L. and M.A.B. contributed to the manuscript. K.M.B. and E.R.T. wrote the manuscript.

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Correspondence to Emily R. Troemel.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Video 1 Legend, Supplementary Table 1, Supplementary Figures 1–6 (PDF 723 kb)

Supplementary Video 1

Time lapse images of a live N. parisii-infected transgenic GFP::LET-413 animal (Same animal as shown in Figure 2b,c). (MOV 15614 kb)

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Balla, K., Luallen, R., Bakowski, M. et al. Cell-to-cell spread of microsporidia causes Caenorhabditis elegans organs to form syncytia. Nat Microbiol 1, 16144 (2016). https://doi.org/10.1038/nmicrobiol.2016.144

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