Year: 2015
Type: article
Abstract: Preventing transmission is an important element of malaria control. However, most of the current available methods to assay for malaria transmission blocking are relatively low throughput and cannot be applied to large chemical libraries. We have developed a high-throughput and cost-effective assay, the Saponin-lysis Sexual Stage Assay (SaLSSA), for identifying small molecules with transmission-blocking capacity. SaLSSA analysis of 13,983 unique compounds uncovered that >90% of well-characterized antimalarials, including endoperoxides and 4-aminoquinolines, as well as compounds active against asexual blood stages, lost most of their killing activity when parasites developed into metabolically quiescent stage V gametocytes. On the other hand, we identified compounds with consistent low nanomolar transmission-blocking activity, some of which showed cross-reactivity against asexual blood and liver stages. The data clearly emphasize substantial physiological differences between sexual and asexual parasites and provide a tool and starting points for the discovery and development of transmission-blocking drugs.
Source: Cell Host & Microbe
Authors: David M. Plouffe, Melanie Wree, Alan Y. Du, Stephan Meister, Fengwu Li, Kailash Patra, Aristea Lubar, Shinji L. Okitsu, Erika L. Flannery, Nobutaka Kato, Olga Tanaseichuk, Eamon Comer, Bin Zhou, Kelli Kuhen, Yingyao Zhou, Didier Leroy, Stuart L. Schreiber, Christina A. Scherer, Joseph Vinetz, Elizabeth A. Winzeler
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Awards: Broad Institute, Inc. - to identify novel/unique small molecules from the Broad Institute’s diversity-oriented synthesis (DOS) library that target the malaria parasite as ..., Amazonian Center of Excellence in Malaria Research, Defining the targets of broad intervention antimalarial agents, Discovery of chemically validated malaria liver stage targets, University of California San Diego - to develop a robust, reproducible set of assays that can be used to identify anti-malarial compounds that prevent the development of gametocytes or...
OpenAlex ID: W2200011422