THE USE OF DROSOPHILA MELANOGASTER AS A MODEL ORGANISM TO STUDY THE EFFECT OF BACTERIAL INFECTION ON HOST SURVIVAL AND METABOLISM

Abstract

Enterobacteriaceae, a large family of facultative anaerobic bacteria, encloses a broad spectrum of bacterial species including Escherichia coli, Salmonella enterica, and Shigella sonnei, that produce enterotoxins and cause gastrointestinal tract diseases. While much is known about the regulation and function of enterotoxins within the intestine of the host; the lack of cheap, practical, and genetically tractable model organisms has restricted the investigation of others facets of this host-pathogen interaction. Our group, among others, has employed Drosophila melanogaster, as a model organism to shed more light on some aspects of host-pathogen interplays. In this project, we addressed the effect of Escherichia coli, Salmonella enterica, and Shigella sonnei infection on altering the metabolic homeostasis of the host. Drosophila melanogaster flies were orally infected with Escherichia coli, Salmonella enterica, or Shigella sonnei, a method that mimics the natural route used by enteric pathogens to gain access to the gastrointestinal tract in humans. The results of our study revealed that both Escherichia coli and Shigella sonnei pathogens were capable of colonizing the host gut, resulting in a reduction in the life span of the infected host. Escherichia coli and Shigella sonnei infected flies also exhibited altered metabolic profiles including lipid droplets deprivation from their fat body (normal lipid storage organ in flies), irregular accumulation of lipid droplets in their gut, and significant elevation of systemic glucose and triglyceride levels. These metabolic alterations could be mechanistically attributed to the differential down-regulation in the expression of metabolic peptide hormones (Allatostatin A, Diuretic hormone 31, and Tachykinin) detected in the gut of Escherichia coli and Shigella sonnei infected flies. Salmonella enterica; however, was unable to colonize the gut of the host; and therefore, Salmonella enterica infected flies exhibited a relatively normal metabolic status as that of non infected flies. Gaining a proper mechanistic understanding of infection-induced metabolic alterations helps in modulating the pathogenesis of gastrointestinal tract diseases in a host and opens up for promising therapeutic approaches for infection induced metabolic disorders