Related Experiment Video
Updated: Jul 19, 2026
Systemic Bacterial Infection and Immune Defense Phenotypes in Drosophila Melanogaster
Published on: May 13, 2015
Akt and FOXO dysregulation contribute to infection-induced wasting in Drosophila
Marc S Dionne1, Linh N Pham, Mimi Shirasu-Hiza
1Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-5124, USA.
Background:
Studies in Drosophila have taught us a great deal about how animals regulate the immediate innate immune response, but we still know little about how infections cause pathology. Here, we examine the pathogenesis associated with Mycobacterium marinum infection in the fly. M. marinum is closely related to M. tuberculosis, which causes tuberculosis in people.
Results:
A microarray analysis showed that metabolism is profoundly affected in M. marinum-infected flies. A genetic screen identified foxo mutants as slower-dying after infection than wild-type flies. FOXO activity is inhibited by the insulin effector kinase Akt; we show that Akt activation is systemically reduced as a result of M. marinum infection. Finally, we show that flies infected with Mycobacterium marinum undergo a process like wasting: They progressively lose metabolic stores, in the form of fat and glycogen. They also become hyperglycemic. In contrast, foxo mutants exhibit less wasting.
Conclusions:
In people, many infections--including tuberculosis--can cause wasting, much as we see in Drosophila. Our study is the first examination of the metabolic consequences of infection in a genetically tractable invertebrate and gives insight into the metabolic consequences of mycobacterial infection, implicating impaired insulin signaling as a key mediator of these events. These results suggest that the fly can be used to study more than the immediate innate immune response to infection; it can also be used to understand the physiological consequences of infection and the immune response.
Insights
Mycobacterium marinum infection in Drosophila causes metabolic wasting and hyperglycemia by impairing insulin signaling. Foxo mutants show reduced wasting, indicating its role in infection pathology.
Area of Science:
- Infectious disease pathology
- Metabolic regulation
- Drosophila melanogaster as a model organism
Background:
- Drosophila models innate immunity but not infection pathology.
- Mycobacterium marinum infection in flies is poorly understood.
- M. marinum is closely related to M. tuberculosis, the human tuberculosis pathogen.
Purpose of the Study:
- To investigate the pathogenesis of Mycobacterium marinum infection in Drosophila.
- To understand the metabolic consequences of M. marinum infection.
- To explore the role of insulin signaling in infection-induced pathology.
Main Methods:
- Microarray analysis to assess gene expression changes.
- Genetic screen using foxo mutants.
- Measurement of Akt activation and metabolic stores (fat, glycogen).
- Observation of hyperglycemia and wasting phenotypes.
Main Results:
- M. marinum infection profoundly affects fly metabolism.
- foxo mutants exhibit delayed mortality and reduced wasting.
- Akt activation is systemically reduced during infection.
- Infected flies display wasting, fat/glycogen loss, and hyperglycemia.
Conclusions:
- Drosophila serves as a model for studying infection-induced metabolic wasting.
- Impaired insulin signaling is a key mediator of mycobacterial infection consequences.
- The fly can model physiological consequences beyond the immediate innate immune response.
