Stochastic variation in the initial phase of bacterial infection predicts the probability of survival in D. melanogaster

A central problem in infection biology is understanding why two individuals exposed to identical infections have different outcomes. We have developed an experimental model where genetically identical, co-housed given identical systemic infections experience different outcomes, with some individuals...

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Bibliographic Details
Published in:eLife 2017-10, Vol.6
Main Authors: Duneau, David, Ferdy, Jean-Baptiste, Revah, Jonathan, Kondolf, Hannah, Ortiz, Gerardo A, Lazzaro, Brian P, Buchon, Nicolas
Format: Article
Language:English
Subjects:
Animals
Bacteria
Bacterial infections
Bacterial Infections - immunology
Bacterial Infections - pathology
Disease Models, Animal
Drosophila
Drosophila melanogaster
Drosophila melanogaster - immunology
Drosophila melanogaster - microbiology
Drosophila melanogaster - physiology
Enterococcus faecalis
Growth rate
Host-Pathogen Interactions
Imd pathway
Immune response
Infections
innate immunity
Insects
inter-individual variation
Microbiology and Infectious Disease
mixture modelling
Parasites
Pathogens
Random variables
Standard deviation
Stochasticity
Survival
Survival Analysis
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Summary:A central problem in infection biology is understanding why two individuals exposed to identical infections have different outcomes. We have developed an experimental model where genetically identical, co-housed given identical systemic infections experience different outcomes, with some individuals succumbing to acute infection while others control the pathogen as an asymptomatic persistent infection. We found that differences in bacterial burden at the time of death did not explain the two outcomes of infection. Inter-individual variation in survival stems from variation in within-host bacterial growth, which is determined by the immune response. We developed a model that captures bacterial growth dynamics and identifies key factors that predict the infection outcome: the rate of bacterial proliferation and the time required for the host to establish an effective immunological control. Our results provide a framework for studying the individual host-pathogen parameters governing the progression of infection and lead ultimately to life or death.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.28298