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An ApiAp2 Transcription Factor with a Dispensable Role in Plasmodium berghei Life Cycle.
- Source :
-
ACS infectious diseases [ACS Infect Dis] 2024 Jun 14; Vol. 10 (6), pp. 1904-1913. Date of Electronic Publication: 2024 May 16. - Publication Year :
- 2024
-
Abstract
- Malaria parasites have a complex life cycle and undergo replication and population expansion within vertebrate hosts and mosquito vectors. These developmental transitions rely on changes in gene expression and chromatin reorganization that result in the activation and silencing of stage-specific genes. The ApiAp2 family of DNA-binding proteins plays an important role in regulating gene expression in malaria parasites. Here, we characterized the ApiAp2 protein in Plasmodium berghei , which we termed Ap2-D. In silico analysis revealed that Ap2-D has three beta-sheets followed by a helix at the C-terminus for DNA binding. Using gene tagging with 3XHA-mCherry, we found that Ap2-D is expressed in Plasmodium blood stages and is present in the parasite cytoplasm and nucleus. Surprisingly, our gene deletion study revealed a completely dispensable role for Ap2-D in the entirety of the P. berghei life cycle. Ap2-D KO parasites were found to grow in the blood successfully and progress through the mosquito midgut and salivary glands. Sporozoites isolated from mosquito salivary glands were infective for hepatocytes and achieved similar patency as WT in mice. We emphasize the importance of genetic validation of antimalarial drug targets before progressing them to drug discovery.
- Subjects :
- Animals
Mice
Malaria parasitology
Transcription Factors genetics
Transcription Factors metabolism
Sporozoites growth & development
Sporozoites metabolism
Sporozoites physiology
Salivary Glands parasitology
Mosquito Vectors parasitology
Female
Anopheles parasitology
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Hepatocytes parasitology
Plasmodium berghei genetics
Plasmodium berghei growth & development
Plasmodium berghei metabolism
Protozoan Proteins genetics
Protozoan Proteins metabolism
Life Cycle Stages
Subjects
Details
- Language :
- English
- ISSN :
- 2373-8227
- Volume :
- 10
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- ACS infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 38752809
- Full Text :
- https://doi.org/10.1021/acsinfecdis.4c00240