000000855 001__ 855
000000855 005__ 20251216173237.0
000000855 0247_ $$2DOI$$a10.6083/M44F1NRN
000000855 037__ $$aETD
000000855 245__ $$aIn vivo evaluation of genetic and pharmacological targeting of the Leshmania donovani polyamine biosynthetic pathway
000000855 260__ $$bOregon Health and Science University
000000855 269__ $$a2012
000000855 336__ $$aThesis
000000855 502__ $$bM.S.
000000855 520__ $$aLeishmania parasites cause leishmaniasis, a neglected tropical disease with limited treatment options and no effective vaccine. Current drugs are toxic, costly, and face resistance, highlighting the need for new targets. This study investigates the polyamine biosynthetic pathway in Leishmania, which differs significantly from mammalian hosts. Using targeted gene replacement, we generated null mutants for four key enzymes (ARG, ODC, SPDSYN, ADOMETDC), confirming the pathway’s essential role in parasite survival and infectivity. Oral supplementation and pharmacologic inhibition demonstrated that polyamine metabolism can be nutritionally or chemically targeted, supporting its potential as a therapeutic strategy against leishmaniasis.
000000855 540__ $$fCC BY
000000855 542__ $$fIn copyright - single owner
000000855 650__ $$aDrug Delivery Systems$$029171
000000855 650__ $$aLeishmania donovani$$021391
000000855 650__ $$aLeishmaniasis$$021394
000000855 650__ $$aLeishmania$$021389
000000855 650__ $$aPolyamines$$024359
000000855 6531_ $$adrug targeting
000000855 691__ $$aSchool of Medicine$$041369
000000855 692__ $$aDepartment of Molecular Microbiology and Immunology$$041429
000000855 7001_ $$aOlenyik, Tamara$$uOregon Health and Science University$$041354
000000855 7201_ $$aUllman, Buddy$$uOregon Health and Science University$$041354$$7Personal$$eAdvisor$$eMentor
000000855 8564_ $$9e5d815b7-552a-41aa-a476-8ec9440413f6$$s1454995$$uhttps://digitalcollections.ohsu.edu/record/855/files/858_etd.pdf$$ePublic$$2071b1a65294e0d7100dac43dab572af1$$31
000000855 905__ $$a/rest/prod/kd/17/cs/90/kd17cs909
000000855 909CO $$ooai:digitalcollections.ohsu.edu:855$$pstudent-work
000000855 980__ $$aTheses and Dissertations