Pattern Recognition System that Monitors Disease-Causing Bacteria in C. elegans
Published:29 Mar.2023 Source:German Center for Infection Research
A study published in Immunity by physician-scientist Read Pukkila-Worley, MD, and MD/PhD students Nicholas D. Peterson and Samantha Y. Tse describes a new manner of detecting microbial infection that intercepts pathogen-derived signals of growth to assess the relative threat of virulent bacteria. A nuclear hormone receptor in the nematode C. elegans senses a toxic metabolite produced by the bacterial pathogen Pseudomonas aeruginosa to activate innate immunity. These data reveal an ancient strategy that informs the origins of pathogen detection and may be among the most primordial forms of immune sensing in animals.
"Our research adds to our understanding of how hosts differentiate between beneficial and harmful bacteria, which teaches us something important about how our immune systems evolved," said Dr. Pukkila-Worley, associate professor of medicine.
Distinguishing potentially harmful pathogens from benign microorganisms is one of the primary functions of the innate immune system in all animals. This is particularly important for nematodes, such as C. elegans -- the transparent microscopic worm often used as a model organism to study genetics and gene function -- that consume bacteria as their food source.
Working with Pseudomonas aeruginosa, a bacteria that commonly infects immune-compromised patients in the hospital and is increasingly resistant to standard antibiotic treatments, Pukkila-Worley and colleagues performed a series of genetic screens with mutant bacteria, one-by-one, to see if any impacted the innate immune system response in C. elegans.
They found that bacteria that cannot produce a specific phenazine metabolite were able to avoid detection by the innate immune system, suggesting that the bacterial phenazine metabolite was sensed to activate innate immunity.