The human pathogen, Schistosoma mansoni, lacks the cognate sequence for human telomerase reverse transcriptase (hTERT) and relies on the snail host, Biomphalaria glabrata homologous enzyme for its intra-molluscan development.

Abstract

The human telomerase reverse transcriptase (hTERT) is the catalytic sub-unit of the ribonuclear protein, telomerase. Together with telomerase RNA, the enzyme complex participates in the maintenance of telomeres at the proximal ends of chromosomes, adding species-specific repeats to the 3’end of the telomere. The regulation of hTERT is tightly linked to the cell cycle and cell differentiation states governing either malignancy or senescence, making it a prospective therapeutic target of cell proliferation in cancer. Malignancy behaves like a parasitic disease in that it only progresses by depending on biochemical and molecular pathways of the host. The snail host/schistosome relationship provides a facile model to examine the regulation of the cancer transcriptome, such as the gastropod homolog of hTERT. To test this hypothesis in relation to the development of larval Schistosoma mansoni in the Biomphalaria glabrata, we utilized an in-silico approach to identify the hTERT homolog of B. glabrata. The human hTERT amino acid sequence (ID 014746) shows a strong homology (E-value of 2e86) to the B. glabrata ortholog (733 amino acids, accession XP_013074763.1). BLASTp analyses using S. mansoni as the query suggested that the parasite lacks a cognate TERT. To study the regulation of the snail-like hTERT in relation to schistosome development, transcriptome analysis was performed which revealed a temporal regulation of the telomerase before and during S. mansoni infection, with an upregulation of B. glabrata hTERT transcription evident by 30 minutes after exposure to the parasite. The anti-telomerase drugs, BPPA and BIBR at 100 ng/mL before infection blocked shedding of parasite cercariae. These findings indicate that the schistosome may rely on the telomerase of its host for asexual reproduction, development and proliferation.