M Knight3; N Pels3; O Elhelu3; S Parn3; G Rinaldi2; V Mann1; P Brindley1;
1 The George Washington University, United States; 2 Wellcome Sanger Institute, UK; 3 University of the District of Columbia, United States
DiscussionThe human telomerase reverse transcriptase, hTERT, is the catalytic sub-unit of telomerase. Together with telomerase RNA, the enzyme complex participates in the maintenance of telomeres at the proximal ends of chromosomes. The regulation of hTERT is tightly linked to cell growth states governing either malignancy or senescence and is a prospective therapeutic target in cancer. Malignancy and parasitic disease share many characteristics, such that we posit that the snail host/schistosome relationship provides a facile model to examine the regulation of transcription of cancer-related genes including the snail ortholog of hTERT. To test the hypothesis in relation the development of larval Schistosoma mansoni in the snail Biomphalaria glabrata, we utilized an in-silico approach to identify the snail hTERT ortholog. From the comparative analysis of the human hTERT amino acid sequence (ID 014746) to the B. glabrata ortholog (733 amino acids, accession XP_013074763.1), a strong homology was evident between amino acid sequences of the telomerase of both species (E-value of 2e-86). BLASTp searches using Schistosoma mansoni as the query suggest that the parasite lacks a putative hTERT, even though the parasite chromosomes do possess telomeres. Concerning the regulation of the snail hTERT ortholog in relation to schistosome intra snail development, real time qPCR analysis revealed temporal regulation of B. glabrata hTERT before and after S. mansoni infection in the snail, with upregulation of B. glabrata hTERT transcription 18 hours after schistosome infection. Treatment of snails with the anti-telomerase drugs before infection blocked subsequent cercarial development. These findings suggest that schistosomes rely on the snail telomerase for productive infection establishment and parasite transmission.