Black sea cucumber (Holothuria atra Jaeger, 1833) rescues Pseudomonas aeruginosa-infected Caenorhabditis elegans via reduction of pathogen virulence factors and enhancement of host immunity

Abstract

Materials and methods:Here, we utilized the Caenorhabditis elegans-P. aeruginosa 43 infection model to assess the anti-infective properties of H. atra. We conducted the C. 44 elegans-P. aeruginosa slow killing assay to isolate a fraction with capable of conferring 45 survival to pathogen-infected worms, followed by a series of tests to assess the 46 anti-virulence and immune-related properties of the sea cucumber bioactive fraction. 47 Results: The H. atra methanol extract improved survival of infected worms without 48 affecting pathogen viability. Further extraction and assays sequestered a fraction with 49 significant anti-infective activities and was able to attenuate the secretion of virulence 50 factors and biofilm formation. Treatment of P. aeruginosa-infected transgenic lys-7::GFP 51 worms with this fraction also restored the repressed expression of host lys-7, a defense 52 enzyme. QTOF-LCMS analysis of this fraction revealed the presence of 53 aspidospermatidine, an indole alkaloid and inosine. 54 Conclusion: Collectively, results shows that H. atra confers survival advantage against P. 55 aeruginosa infection through inhibition of pathogen virulence and the restitution of host 56 lys-7 expression.57