An intestinally secreted host factor promotes microsporidia invasion of C. elegans

Abstract

Microsporidia are ubiquitous obligate intracellular pathogens of animals. These parasites often infect hosts through an oral route, but little is known about the function of host intestinal proteins that facilitate microsporidia invasion. To identify such factors necessary for infection by Nematocida parisii, a natural microsporidian pathogen of Caenorhabditis elegans, we performed a forward genetic screen to identify mutant animals that have a Fitness Advantage with Nematocida (Fawn). We isolated four fawn mutants that are resistant to Nematocida infection and contain mutations in T14E8.4, which we renamed aaim-1 (Antibacterial and Aids invasion by Microsporidia). Expression of AAIM-1 in the intestine of aaim-1 animals restores N. parisii infectivity and this rescue of infectivity is dependent upon AAIM-1 secretion. N. parisii spores in aaim-1 animals are improperly oriented in the intestinal lumen, leading to reduced levels of parasite invasion. Conversely, aaim-1 mutants display both increased colonization and susceptibility to the bacterial pathogen Pseudomonas aeruginosa and overexpression of AAIM-1 reduces P. aeruginosa colonization. Competitive fitness assays show that aaim-1 mutants are favoured in the presence of N. parisii but disadvantaged on P. aeruginosa compared to wild type animals. Together, this work demonstrates how microsporidia exploits a secreted protein to promote host invasion. Our results also suggest evolutionary trade-offs may exist to optimizing host defense against multiple classes of pathogens.

Genomic and phenotypic evolution of nematode-infecting microsporidia

“…N2 and aaim-1 mutants (kea22 and kea28) 23 were infected with N. cider (4 million spores) as described above. To quantify pathogen burden within animals (GFP), regions of interest were .…”

“…The copyright holder for this preprint this version posted August 28, 2022. ; https://doi.org/10.1101/2022.08. 28.505597 doi: bioRxiv preprint infection of a host, host immune responses to infection, and identify inhibitors of microsporidian infection [21][22][23][24][25][26][27][28] . Additional species that infect the intestine, N. ausubeli and N. ironsii, have also been identified 20,21 .…”

High-throughput phenotyping of infection by diverse microsporidia species reveals a wildC. elegansstrain with opposing resistance and susceptibility traits

“…Several studies have shown that microsporidia can affect host population dynamics and evolution. Microsporidia have been suggested to influence the composition of Caenorhabditis elegans genotypes and resistant strains can outcompete sensitive ones in just a few generations [18][19][20]. In competition experiments with over a dozen isolates of Daphnia magna, different microsporidia species have been shown to select for specific strains [21,22].…”

High-throughput small molecule screen identifies inhibitors of microsporidia invasion and proliferation in C. elegans

“…Compounds that displayed strong activity against microsporidia infection in the continuous infection assays, but not the pulse-chase infections, may be preventing invasion by inhibiting spore firing. In C. elegans , N. parisii spores are ingested, and spore firing is triggered in the intestinal lumen (27, 48). To test if any compounds interfere with this process, we performed spore firing assays on the 7 compounds with the strongest effect in the continuous infection assays (Fig.…”