Staphylococcus aureus-induced degeneration of nociceptive neurons in Caenorhabditis elegans

The nervous system senses microbial signals to influence host defense. Pain-sensing nociceptor neurons are key regulators of the host response to infection, but how they perceive infections is not well understood. Using Caenorhabditis elegans as a tractable model host that shares many features with mammalian systems, we investigated the effects of infection on nociceptor function in vivo.

In vivo intracellular Ca²⁺ imaging of C. elegans nociceptor ASH neurons revealed a drastic reduction in ASH responses to aversive stimuli in Staphylococcus aureus-infected animals compared to noninfected controls. Morphological examination revealed that ASH neurons lost integrity in the sensory processes reaching the mouth. Neighboring neurons did not show this pathogen-induced neurite pathology (PaIN) phenotype. During acute pathogen exposure, ASH neurons experience Ca²⁺ suppression. Genetic analysis indicated that apoptosis, necrosis, ferroptosis, and autophagy are not essential for the PaIN phenotype. Conversely, loss of the evolutionarily conserved stress-response transcription factor HLH-30/TFEB decreased the penetrance of ASH PaIN by approximately 50%. Additionally, infected animals exhibited defective ASH-mediated evasive behaviors, suggesting that the S. aureus-triggered reduction in ASH activation and morphological degeneration is physiologically relevant.

S. aureus damages nociceptor integrity in C. elegans: ASH neurons experience acute Ca²⁺ suppression-most pronounced with stationary-phase cultures-and extended exposure leads to structural damage and decreased avoidance behavior. This connection between pathogen physiology and circuit failure suggests that infection-evoked nociceptor PaIN may contribute to sensory dysfunction, highlighting the need to identify the responsible bacterial factor(s) and their host targets.