The regulation of gene expression during Plasmodium yoelii host-to-vector transmission
Restricted (Penn State Only)
- Author:
- Rios, Kelly
- Graduate Program:
- Biochemistry, Microbiology, and Molecular Biology (PHD)
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- August 23, 2022
- Committee Members:
- Sarah Assmann, Outside Unit Member
Scott Lindner, Chair & Dissertation Advisor
Manuel Llinas, Major Field Member
Philip Bevilacqua, Major Field Member
Joyce Jose, Outside Field Member
Ken Keiler, Program Head/Chair - Keywords:
- malaria
translational repression
parasitology
Plasmodium yoelii - Abstract:
- Malaria is a widespread mosquito-borne disease caused by infection with eukaryotic Plasmodium parasites. Current treatment and control measures are challenged by mosquito resistance to insecticides and the rapid development of parasite resistance to antimalarial therapeutics targeting blood-stage parasites. Additional intervention targets and strategies need to be identified and developed to be used in combination with existing approaches reduce the burden of malaria. Disrupting essential processes in parasite transmission would reduce overall malaria incidence by preventing infection altogether. This could be achieved directly by preventing parasite invasion or development in host hepatocytes, or indirectly by limiting parasite transmission and development in the mosquito. Therapeutics or vaccines targeting host-to-vector transmission would not protect a treated individual against new infections, but would prevent community spread of disease, thereby reducing overall malaria cases. To explore unique developmental processes essential for host-to-vector transmission, transmission-stage gametocytes can be isolated from asexual blood-stage parasites. One prominent way that rodent-infectious gametocytes are enriched from other blood-stage parasites during in vivo infection is the use of sulfadiazine to selectively kill actively replicating asexual blood stages, leaving only gametocytes in circulation to be collected. However, it has not been clearly demonstrated that P. yoelii or P. berghei gametocytes are unaffected by this drug treatment. Therefore, as described in Chapter 2, I have characterized the effect of sulfadiazine treatment on gametocyte transmissibility and have found that sulfadiazine exposure in the mammalian host or the mosquito vector in fact does limit transmission. Because of these unexpected effects on parasite transmission that were observed, I pursued an alternative approach, fluorescence-activated cell sorting (FACS), that is better suited for the enrichment of less perturbed gametocytes and zygotes for the investigation of gene expression regulation during host-to-vector transmission in Chapter 3. We used the enriched female gametocytes and zygotes for comparative transcriptomic and proteomic studies to demonstrate the control of translational repression during host-to-vector transmission, and for the first time characterize the widespread release of translational repression following fertilization. Together, this work characterized the effect of sulfadiazine exposure on P. yoelii transmission to mosquitoes, and the release of translational repression during parasite host-to-vector transmission.