טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentAlterzon Sharon
SubjectIdentification of Dihydropyrimidine Dehydrogenase as
a Virulence Factor Essential for the Survival of
Entamoeba Histolytica in Glucose-Poor
Envirinments
DepartmentDepartment of Medicine
Supervisor Professor Serge Ankri
Full Thesis textFull thesis text - English Version


Abstract

Adaptation to nutritional changes is a key feature for successful survival of a pathogen within its host. The protozoan parasite Entamoeba histolytica normally colonizes the human colon and in rare occasions, this parasite spread to distant organs, such as the liver. E. histolytica obtains most of its energy from the fermentation of glucose into ethanol. In this study, we were interested to know how this parasite reacts to changes in glucose availability and we addressed this issue by performing a DNA microarray analysis of gene expression. Results show that parasites that were adapted to growth in absence of glucose increased their virulence and altered the transcription of several genes. One of these genes is the dihydropyrimidine dehydrogenase (DPD), which is involved in degradation of pyrimidines.  We showed that this gene is crucial for the parasite’s growth when the availability of glucose is limited. These data contribute to our understanding of the parasite’s ability to survive in glucose poor environments and reveal a new role for the DPD enzyme. Recent data indicates that DPD expression is down regulated in the presence of glucose rather than being up regulated during glucose starvation. Currently one protein (SPT6 homologue) that binds the DPD promoter is suspected to regulate negatively DPD expression in the presence of glucose.