Teitl: Life cycle, biochemistry and chemotherapy of Spironucleus vortens

Arianwyr
Engineering and Physical Sciences Research Council

Prif Ymchwiliwr

Cyd-Ymchwilwyr
Cable, Joanne

Manylion y Prosiect
Dyddiad dechrau: 01.10.2009
Dyddiad gorffen: 27.05.2013
Crynodeb



Spironucleus is
an opportunistic protozoan parasite capable of causing devastating losses in
the production of both ornamental and food fish. Control of infection outbreaks
is problematic due to restrictions on the use of chemotherapeutics and rapid
parasite transmission amongst fish. This PhD investigated the life cycle,
biochemistry and chemotherapy of Spironucleus vortens. Direct transmission of
S. vortens was found to be facilitated by the trophozoite form, information
which may be applied in aquaculture to prevent infection outbreaks. No S.
vortens cysts were observed in vitro or in vivo and trophozoites were able to
survive for prolonged periods in the faeces of angelfish. This novel finding
facilitated development of a non-invasive method to quantify the degree of
intestinal colonization in the host, which was then applied to determine the
efficacy of new and existing chemotherapeutics against S. vortens in vivo.
Garlic-derived compounds were shown to be realistic alternatives to the current
drug of choice, metronidazole, in the treatment of Spironucleosis in fish.
Synergy between metronidazole and the garlic-derived compound, ajoene, was also
observed in vitro and in vivo. The mode of action of metronidazole and
garlic-derivatives involved disruption of S. vortens intracellular redox
balance, a pivotal cellular process which ensures normal cellular function and
survival. Further biochemical investigations into the antioxidant defence
system (consisting of glutathione, thioredoxin and superoxide dismutase) as
well as the carbohydrate and amino acid metabolism of S. vortens provided
greater understanding of the success of this organism as a parasite. This is
reflected in its ability to withstand fluctuations in O2 and nutrition during
key pathogenic stages of its life cycle, including extra-intestinal systemic
infection and transmission to a new host.


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