RESUMEN
Caenorhabditis elegans are an important model system for research on host-microbe interaction. Their rapid life cycle, short lifespan, and transparent body structure allow simple quantification of microbial load and the influence of microbial exposure on host survival. C. elegans host-microbe interaction studies typically examine group survival and infection severity at fixed timepoints. Here we present an imaging pipeline, Systematic Imaging of Caenorhabditis Killing Organisms (SICKO), that allows longitudinal characterization of microbes colonizing isolated C. elegans, enabling dynamic tracking of tissue colonization and host survival in the same animals. Using SICKO, we show that Escherichia coli or Pseudomonas aeruginosa gut colonization dramatically shortens C. elegans lifespan and that immunodeficient animals lacking pmk-1 are more susceptible to colonization but display similar colony growth relative to wild type. SICKO opens new avenues for detailed research into bacterial pathogenesis, the benefits of probiotics, and the role of the microbiome in host health.
RESUMEN
3-hydroxyanthranilic acid (3HAA) is considered to be a fleeting metabolic intermediate along tryptophan catabolism through the kynurenine pathway. 3HAA and the rest of the kynurenine pathway have been linked to immune response in mammals yet whether it is detrimental or advantageous is a point of contention. Recently we have shown that accumulation of this metabolite, either through supplementation or prevention of its degradation, extends healthy lifespan in C. elegans and mice, while the mechanism remained unknown. Utilizing C. elegans as a model we investigate how 3HAA and haao-1 inhibition impact the host and the potential pathogens. What we find is that 3HAA improves host immune function with aging and serves as an antimicrobial against gram-negative bacteria. Regulation of 3HAA's antimicrobial activity is accomplished via tissue separation. 3HAA is synthesized in the C. elegans hypodermal tissue, localized to the site of pathogen interaction within the gut granules, and degraded in the neuronal cells. This tissue separation creates a new possible function for 3HAA that may give insight to a larger evolutionarily conserved function within the immune response.