Jager, V.D. de (2018) Drosophila Melanogaster as a model organism to study long-term mortality after sepsis. thesis, Medicine.
Full text available on request.Abstract
Sepsis, an immense systemic inflammatory response to an infection commonly known as ‘blood poisoning’, has a high in-hospital mortality risk, carries large economical costs due to hospital care and loss of labour force after hospitalization. The incidence of sepsis is rising, presumably due to aging of the population and increased incidences of chronic health conditions. Patients surviving sepsis have a decreased life expectancy and are more likely to develop (chronic) diseases, but long-term follow-up studies are seldomly conducted due to the high costs, the labour-investment and the long duration. The pathophysiology that underlies reduction of lifespan following sepsis remains unknown. However, mitochondrial dysfunction plays a key role in sepsis and is associated with sepsis severity and mortality. In this study, we used the Drosophila Melanogaster (fruit fly) to develop a model to mimic human sepsis with Staphylococcus Aureus as bacterial pathogen, and studied mitochondrial function and long-term outcome after sepsis. Similar to human sepsis, septic flies developed mitochondrial dysfunction as reflected by lowered membrane potential, decreased levels of ATP, and increased mitochondrial superoxide production. Consistent with clinical outcome in septic patients, septic flies had increased short-term mortality and impaired motility. In addition, flies surviving injection with a high bacterial load had shortened lifespan. Injection of the 6-chromanol Sul-151 at the induction of sepsis increased initial 24-hour survival and climbing motility, but did not affect mitochondrial function. In conclusion, we set up a Drosophila Melanogaster model of sepsis which displays mitochondrial dysfunction, and short-term and long-term survival mimicking key features of human septic patients. This model may not only aid to unravel (part of) the complex pathophysiology of sepsis, but also allow relatively high-throughput screening of pharmacological compounds at low cost to study its effects on short- and long-term consequences of sepsis.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisors: and Bouma dr. H.R.& and Henning, prof. dr. R.H. and Department: Clinical Pharmacy and Pharmacology |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:05 |
| Last Modified: | 25 Jun 2020 11:05 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2519 |
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