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Systemic Bacterial Infection and Immune Defense Phenotypes in Drosophila Melanogaster
Published on: May 13, 2015
Secreted Bacterial Effectors and Host-Produced Eiger/TNF Drive Death in aSalmonella-Infected Fruit Fly
Stephanie M Brandt1, Marc S Dionne, Ranjiv S Khush
1Department of Microbiology and Immunology, Stanford University Stanford, California United States of America.
Abstract:
Death by infection is often as much due to the host's reaction as it is to the direct result of microbial action. Here we identify genes in both the host and microbe that are involved in the pathogenesis of infection and disease in Drosophila melanogaster challenged with Salmonella enterica serovartyphimurium (S. typhimurium). We demonstrate that wild-typeS. typhimurium causes a lethal systemic infection when injected into the hemocoel of D. melanogaster. Deletion of the gene encoding the secreted bacterial effect or Salmonella leucine-rich (PslrP)changes an acute and lethal infection to one that is persistent and less deadly. We propose a model in which Salmonella secreted effectors stimulate the fly and thus cause an immune response that is damaging both to the bacteria and, subsequently, to the host. In support of this model, we show that mutations in the fly gene eiger, a TNF homolog, delay the lethality of Salmonella infection. These results suggest that S. typhimurium-infected flies die from a condition that resembles TNF-induced metabolic collapse in vertebrates. This idea provides us with a new model to study shock-like biology in a genetically manipulable host. In addition, it allows us to study the difference in pathways followed by a microbe when producing an acute or persistent infection.
Insights
Salmonella typhimurium infection in fruit flies (Drosophila melanogaster) can be lethal due to the host
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- Infectious diseases involve complex interactions between microbial pathogens and host immune responses.
- Host reactions can significantly contribute to disease severity, sometimes more than direct microbial damage.
Purpose of the Study:
- To identify host and microbial genes influencing pathogenesis during Salmonella enterica serovar Typhimurium (S. typhimurium) infection in Drosophila melanogaster.
- To investigate the mechanisms underlying lethal versus persistent infection outcomes.
Main Methods:
- Infection of Drosophila melanogaster with wild-type and mutant S. typhimurium strains.
- Genetic analysis of host (eiger gene) and bacterial (PslrP gene) factors.
- Observation and comparison of infection lethality and persistence.
Main Results:
- Wild-type S. typhimurium causes lethal systemic infection in fruit flies.
- Deletion of the bacterial Salmonella leucine-rich effector gene (PslrP) shifts infection from acute and lethal to persistent and less deadly.
- Mutations in the fly gene eiger (a TNF homolog) delay infection lethality.
Conclusions:
- Salmonella secreted effectors may trigger a damaging host immune response, leading to host death.
- Fruit fly infection models mimic aspects of TNF-induced metabolic collapse seen in vertebrates.
- This study provides a model for investigating acute versus persistent infection pathways and shock-like biology.
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