Epithelial cell NOD1/IRGM recruits STX17 to Neisseria gonorrhoeae-containing endosomes to initiate lysosomal degradation.

Neisseria gonorrhoeae establishes tight interactions with mucosal epithelia through activity of its type IV pilus, while pilus-retraction forces furthermore activate autophagic responses towards invading gonococci. Here we studied pilus-independent epithelial cell responses and showed that pilus-negative gonococci residing in early and late endosomes are detected and targeted by nucleotide-binding oligomerization domain 1 (NOD1). NOD1 subsequently forms a complex with immunity-related guanosine triphosphatase M (IRGM) and autophagy related 16 like 1 (ATG16L1) to activate autophagy and recruit microtubule-associated protein light chain 3 (LC3) to the intracellular bacteria. IRGM furthermore directly recruits syntaxin 17 (STX17), which is able to form tethering complexes with the lysosome. Importantly, IRGM/STX17 interactions are enhanced by LC3, but still observed at lower levels in an LC3 knock-out cell line. These findings demonstrate key roles for NOD1 and IRGM in sensing of intracellular N. gonorrhoeae and subsequent directing of the bacterium to the lysosome for degradation.