The small GTPase RAB-11 directs polarized exocytosis of the intracellular pathogen N. parisii for fecal-oral transmission from C. elegans.
Pathogen exit is a key stage in the spread and propagation of infectious disease, with the fecal-oral route being a common mode of disease transmission. However, it is poorly understood which molecular pathways provide the major modes for intracellular pathogen exit and fecal-oral transmission in vivo. Here, we use the transparent nematode Caenorhabditis elegans to investigate intestinal cell exit and fecal-oral transmission by the natural intracellular pathogen Nematocida parisii, which is a recently identified species of microsporidia. We show that N. parisii exits from polarized host intestinal cells by co-opting the host vesicle trafficking system and escaping into the lumen. Using a genetic screen, we identified components of the host endocytic recycling pathway that are required for N. parisii spore exit via exocytosis. In particular, we show that the small GTPase RAB-11 localizes to apical spores, is required for spore-containing compartments to fuse with the apical plasma membrane, and is required for spore exit. In addition, we find that RAB-11-deficient animals exhibit impaired contagiousness, supporting an in vivo role for this host trafficking factor in microsporidia disease transmission. Altogether, these findings provide an in vivo example of the major mode of exit used by a natural pathogen for disease spread via fecal-oral transmission.
Division of Biological Sciences, Section of Cell and Developmental Biology, University of California at San Diego, La Jolla, CA 92093.
Suzannah C
SC
Szumowski
Division of Biological Sciences, Section of Cell and Developmental Biology, University of California at San Diego, La Jolla, CA 92093.
Michael R
MR
Botts
Division of Biological Sciences, Section of Cell and Developmental Biology, University of California at San Diego, La Jolla, CA 92093.
John J
JJ
Popovich
Division of Biological Sciences, Section of Cell and Developmental Biology, University of California at San Diego, La Jolla, CA 92093.
Margery G
MG
Smelkinson
Division of Biological Sciences, Section of Cell and Developmental Biology, University of California at San Diego, La Jolla, CA 92093 etroemel@ucsd.edu.
Emily R
ER
Troemel
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002451:Cell Compartmentation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D016764:Cell Polarity / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D016814:Microsporidia / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D013172:Spores, Fungal / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D033921:Vesicular Transport Proteins; C558453:rab-11.1 protein, C elegans