Abstract
BackgroundFilarial nematodes are important pathogens in the tropics transmitted to humans via the bite of blood sucking arthropod vectors. The molecular mechanisms underpinning survival and differentiation of these parasites following transmission are poorly understood. microRNAs are small non-coding RNA molecules that regulate target mRNAs and we set out to investigate whether they play a role in the infection event.ResultsmicroRNAs differentially expressed during the early post-infective stages of Brugia pahangi L3 were identified by microarray analysis. One of these, bpa-miR-5364, was selected for further study as it is upregulated ~12-fold at 24 hours post-infection, is specific to clade III nematodes, and is a novel member of the let-7 family, which are known to have key developmental functions in the free-living nematode Caenorhabditis elegans. Predicted mRNA targets of bpa-miR-5364 were identified using bioinformatics and comparative genomics approaches that relied on the conservation of miR-5364 binding sites in the orthologous mRNAs of other filarial nematodes. Finally, we confirmed the interaction between bpa-miR-5364 and three of its predicted targets using a dual luciferase assay.ConclusionsThese data provide new insight into the molecular mechanisms underpinning the transmission of third stage larvae of filarial nematodes from vector to mammal. This study is the first to identify parasitic nematode mRNAs that are verified targets of specific microRNAs and demonstrates that post-transcriptional control of gene expression via stage-specific expression of microRNAs may be important in the success of filarial infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1536-y) contains supplementary material, which is available to authorized users.
Highlights
Filarial nematodes are important pathogens in the tropics transmitted to humans via the bite of blood sucking arthropod vectors
* Correspondence: alan.winter@glasgow.ac.uk; collette.britton@glasgow.ac.uk; eileen.devaney@glasgow.ac.uk 1Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Bearsden Road, Glasgow G61 1QH, UK Full list of author information is available at the end of the article, which are small (~22 nucleotide) noncoding RNAs that regulate gene expression in animals, plants and viruses. miRNAs bind to complementary sequences, often in the 3′ untranslated region (UTR) of mRNAs, leading to translational repression and mRNA destabilisation [1]. miRNAs are essential during development in the free-living nematode Caenorhabditis elegans, with functions in developmental timing [2,3,4], lifespan and stress responses [5,6], and embryogenesis [7,8]
We recently identified 104 miRNAs from the filarial nematode Brugia pahangi [14], the sister species to the human pathogen B. malayi
Summary
Filarial nematodes are important pathogens in the tropics transmitted to humans via the bite of blood sucking arthropod vectors. The molecular mechanisms by which eukaryotic pathogens infect their hosts remain key questions in infection biology, as improved understanding of these events could lead to new methods of control. This is so for vector-borne parasites, where the ability to survive and differentiate within the new environment of a mammalian host is critical for successful transmission. C. elegans lin-4, the first miRNA to be identified [2], regulates developmental switching during the early larval stages (L1 and L2) by repressing the heterochronic proteins LIN-14 [9] and LIN-28 [10], allowing epidermal cell fate transitions. C. elegans let-7 was the second miRNA to be identified and acts from the L3
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