[
International Worm Meeting,
2021]
Commensal microorganisms that colonize host surfaces can modulate susceptibility to infection. This can occur through direct inhibition of pathogen growth via competitive exclusion, or by modulation of the host environment to prevent pathogen dissemination and infection-mediated damage. However, understanding the mechanisms underlying these interactions is challenging due to the complexity of the microbiome. Here, we investigate the influence of human respiratory tract microbiota isolates on C. elegans susceptibility to Pseudomonas aeruginosa infection. Identifying isolates that differentially regulate resistance to infection will provide insight into how particular strains isolated from the human microbiome may improve or worsen infection outcomes. In order to identify microbiotal isolates that can protect C. elegans from P. aeruginosa infection, a screen of bacterial isolates derived from the human respiratory tract was carried out using a liquid-based infection assay. Animals were first exposed to lawns of individual microbiotal isolates during development, prior to infection with a pathogenic strain of P. aeruginosa, PA14. We find that pre-exposure to two non-pathogenic isolates of P. aeruginosa is able to increase survival during PA14 liquid killing, compared to animals pre-exposed to E. coli OP50. This protective phenotype can also be induced by other mildly pathogenic strains of P. aeruginosa, including a laboratory strain with genetically attenuated virulence, PAO1deltavfr. Current work focuses on identifying host pathways underlying this protective phenotype, as well as how previous exposure to other Gram-negative pathogens can regulate P. aeruginosa infection outcomes in C. elegans.