부산대학교 도서관

국외단행본

Learning on the Fly: Adverse Effects of High Sugar Diets and Metabolic Consequences of Infection [electronic resource].

Cornell University. Entomology.

[S.l.] : Cornell University. 2024 Ann Arbor : ProQuest Dissertations & Theses , 2024

1 online resource(180 p.)

Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
Includes supplementary digital materials.
Advisor: Lazzaro, Brian.

Thesis (Ph.D.)--Cornell University, 2024.

The immune response to infection stimulates major shifts in metabolic processes to allocate energy to fuel the immune system. Diet quality has significant effects on host physiology and energy stores that can materially impact infection outcomes. High-sugar diets have been negatively associated with health-outcome, including survival to infection in mammals and insects. Organisms are also faced with a diversity of pathogens in their environment, so different pathogens could yield different effects on metabolic stores post-infection. In my dissertation, I first summarize in a review article the known physiological consequences and underlying mechanisms by which innate immune pathways and insulin signaling interact to impact infection resistance in insects. Using the fruit fly Drosophila melanogaster, I then examined two phenomena of how immunity and metabolism interact in the acute phase and chronic phase of infection.In my first data chapter, I investigated which aspects of host and pathogen physiology are impacted by feeding on high-sugar diets to shape infection dynamics. By feeding adult flies' diets that range from 0%-24% sucrose (w/v), I found that increasing the amount of sugar led to a threshold effect of sugar content on infection outcome in a pathogen-dependent manner. Particularly, I found that high-sugar diets led to significantly higher mortality when flies were infected with the Gram-negative bacteria Serratia marcescens and Providencia rettgeri, while diet was not a major factor for surviving infection with the Gram-positive bacteria Enterococcus faecalis and Lactococcus lactis. I further found that only S. marcescens can proliferate faster in the presence of excess sugar. Using Sandwich ELISAs to quantify HA-FLAG tagged antimicrobial peptides, I showed that high-sugar diets can reduce the amount of peptide produced post-infection. I conclude that high-sugar diets can provide a growth advantage to infecting pathogens by a combination of providing excess carbon source and impairing translation of immune effectors like antimicrobial peptides. Overall, this study demonstrates the importance of knowing pathogen-specific nutritional requirements and how host's metabolism and immune system interact when studying the effect of diet on infection dynamics.In my second data chapter, I investigate to what extent do factors like severity of pathogen strain and inoculum dose (low vs high) affect energetic stores in chronically infected flies. Flies that survive the acute phase of bacterial infection then establish a chronic infection evident by carrying a persistent bacterial burden and expression of antimicrobial peptides. I hypothesized that more severe infections lead to the reduction of the energetic stores due to physiological constraints that arise from carrying a high bacterial burden. I found that more severe infections, either by a more virulent strain or a higher inoculum dose of the same species, lead to higher chronic bacterial burden and increased sensitivity to starvation. This increased starvation sensitivity was associated with reduction in the energetic stores of triglyceride and glycogen. Interestingly, infection with high virulent P. rettgeri only reduced glycogen stores while infection high virulent S. marcescens strain reduced both glycogen and triglyceride levels, which could suggest that the host may bias depletion of certain metabolic stores depending on the identity of the infecting pathogen. I found that high virulent Serratia and Providencia infections led to increased gene expression of antimicrobial peptides. However, only for Providencia infections did the observed AMP gene expression correspond to higher production of tagged AMP peptides. This study importantly demonstrates a generalized principle that carrying a higher chronic bacterial load is associated with elevated immune activity, which is consequential to metabolic stores.

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