Cell-cell fusion is a common developmental process in animals that is limited to specialized tissues. Interestingly, cells that do not normally undergo fusion can be induced to do so by pathogens. For example, viruses and bacteria are well-known coordinators of abnormal cell-cell fusion in hosts. Here, we find that infection by an intracellular eukaryotic pathogen causes a dramatic fusion of host cells during the replication phase of its lifecycle. Specifically, when C. elegans is infected by the microsporidian parasite Nematocida parisii, the pathogen grows and fuses intestinal cells as it spreads from cell to cell. We find that intestinal infection by a single N. parisii cell can rapidly grow to dominate the entire organ before differentiating to form new spores, which are the transmissible form of the parasite. We use microscopy to observe infection over time in live animals and find that GFP-labeled LET-413, a marker of basolateral membrane, is disrupted on intestinal cells as N. parisii spreads. Furthermore, by measuring the diffusion of a photoconvertible fluorescent protein we find that the cytoplasmic content of infected intestinal cells becomes shared. These experiments demonstrate that a single infectious event by a eukaryotic pathogen causes the intestine of C. elegans to fuse into a syncytium. We are now performing a forward-genetic screen to identify host factors that underlie this process.
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