UC San Diego

Obligate intracellular pathogens evolve under selective pressure from their host organisms to successfully infect and replicate in host cells. Microsporidia are obligate intracellular pathogens that display evidence of this selective pressure, including severely reduced genomes, loss of true mitochondria, and loss of conserved metabolic pathways. Wild isolates of Caenorhabditis elegans are regularly found with microsporidia infection, allowing for the investigation of natural microsporidia infection processes using a genetic model host. Two such microsporidian species Nematocida parisii and N. sp. 1 exclusively infect and replicate in the intestine of C. elegans leading to phenotypic consequences on the host, including developmental arrest and premature death. Through a targeted RNAi screen, we found several host genes that control infection-induced developmental arrest by N. parisii. We also discovered a new species of microsporidia inside a wild C. elegans isolated near Paris, France with a distinct tissue tropism from N. parisii and N. sp. 1, despite being in the Nematocida genus. This new species infects via host feeding, replicates in multiple tissues, and exits via vulva bursting, leading us to name it N. displodere. This new pathogen displays an complementary tissue tropism to other Nematocida species, as N. displodere is able to infect and proliferate in a broad array of tissues and cells but displays a reduced ability to replicate in the intestine. We found that during infection, Nematocida species can spread from a single host cell across numerous neighboring cells in a tissue, with N. parisii and N. sp. 1 limited to the intestine, and N. displodere capable of spreading in the muscle and epidermis, but mostly limited to a single cell in the intestine. Additionally, we found that N. displodere displays a broader host range than N. parisii but narrower temperature range, with efficient replication for N. displodere limited to temperatures lower than 20°C in all tested host species. Altogether, we characterize a new species of microsporidia, Nematocida displodere, and compare this pathogen to other Nematocida species identified to date, providing a powerful system to study the mechanistic and evolutionary bases of tissue tropism, temperature restriction, and host range of microsporidia.