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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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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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