PLOS Neglected Tropical Diseases
Lymphatic filariasis and onchocerciasis are tropical diseases caused by infections with parasitic nematodes. Resulting chronic diseases can be strongly blinding and disfiguring, and contribute to an entrenched cycle of poverty in affected populations. Ivermectin is one of the pivotal drugs used to control these infections. The mechanism of antifilarial action of the drug is incompletely resolved. It kills circulating larval stages (microfilariae), but only reversibly sterilizes adult worms without killing them. Our limited understanding of the involved mechanisms hampers treatment optimization and sustainability of the efficacy of the drug, and investigations into its pharmacology are of paramount importance. Working with Brugia malayi adult females, we employed RNA sequencing and bioinformatics analyses to identify genes for which expression levels changed as a result of exposure to the drug in vitro. Ivermectin exposure altered the expression of genes that are likely to func- tion in the B. malayi female reproductive system even at the lowest concentration tested. Through several biological pathways, genes involved in meiosis were particularly affected. These findings provide some insight into the mechanisms involved in ivermectin-induced reduction in microfilaria output and impaired fertility, embryogenesis, and larval development.
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Ballesteros, Cristina; Tritten, Lucienne; O'Neill, Maeghan; Burkman, Erica; Zaky, Weam I.; Xia, Jianguo; Moorhead, Andrew; Williams, Steven A.; and Geary, Timothy G., "The Effects of Ivermectin on Brugia malayi Females In Vitro: A Transcriptomic Approach" (2016). Biological Sciences: Faculty Publications, Smith College, Northampton, MA.