Presenter Information

Joshua AsselinFollow

Presentation Type

Oral/Paper Presentation

Abstract

Necrotizing enterocolitis (NEC) is a severe and often life-threatening inflammatory condition of the intestine primarily affecting premature infants. The opportunistic pathogen Cronobacter sakazakii (Cs) has been implicated in NEC. While activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) has been shown to prevent NEC in a mouse model, its potential as a therapeutic target for established NEC remains unclear. We hypothesize here that the AhR ligand indole can reverse Cs-mediated illness in the model organism Caenorhabditis elegans. Our results demonstrate that exposure to live Cs, but not heat-killed Cs, significantly impaired worm motility, demonstrating Cs is an effective pathogen of C. elegans. Treatment of Cs-infected worms with indole improved motility and enhanced survival under heat stress. These effects were dependent on ahr-1, the C. elegans ortholog of the human AHR gene. Finally, wild-type worms infected with Cs maintained higher motility scores and heat stress survival rates than their ahr-1 knockout counterparts, even with no exogenous indole supplied but fed a diet of indole-producing commensal Escherichia coli prior to Cs infection. Our findings indicate that indole enhances health outcomes in Cs-exposed worms, suggesting a potential therapeutic avenue for NEC. Further investigation into AhR ligands could reveal new treatment strategies for managing NEC in premature infants.

Faculty Mentor

Kyle Brawner brawnerkm@lipscomb.edu

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Indole Treatment of C. elegans Rescues Cronobacter sakazakii Induced Illness

Necrotizing enterocolitis (NEC) is a severe and often life-threatening inflammatory condition of the intestine primarily affecting premature infants. The opportunistic pathogen Cronobacter sakazakii (Cs) has been implicated in NEC. While activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) has been shown to prevent NEC in a mouse model, its potential as a therapeutic target for established NEC remains unclear. We hypothesize here that the AhR ligand indole can reverse Cs-mediated illness in the model organism Caenorhabditis elegans. Our results demonstrate that exposure to live Cs, but not heat-killed Cs, significantly impaired worm motility, demonstrating Cs is an effective pathogen of C. elegans. Treatment of Cs-infected worms with indole improved motility and enhanced survival under heat stress. These effects were dependent on ahr-1, the C. elegans ortholog of the human AHR gene. Finally, wild-type worms infected with Cs maintained higher motility scores and heat stress survival rates than their ahr-1 knockout counterparts, even with no exogenous indole supplied but fed a diet of indole-producing commensal Escherichia coli prior to Cs infection. Our findings indicate that indole enhances health outcomes in Cs-exposed worms, suggesting a potential therapeutic avenue for NEC. Further investigation into AhR ligands could reveal new treatment strategies for managing NEC in premature infants.

 

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