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Spatial transcriptomics reveals antiparasitic targets associated with essential behaviors in the human parasite Brugia malayi

View ORCID ProfilePaul M. Airs, Kathy Vaccaro, Kendra J. Gallo, View ORCID ProfileNathalie Dinguirard, Zachary W. Heimark, Nicolas J. Wheeler, View ORCID ProfileJiaye He, View ORCID ProfileKurt R. Weiss, View ORCID ProfileNathan E. Schroeder, View ORCID ProfileJan Huisken, View ORCID ProfileMostafa Zamanian
doi: https://doi.org/10.1101/2021.08.24.456436
Paul M. Airs
1Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI USA
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Kathy Vaccaro
1Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI USA
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Kendra J. Gallo
1Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI USA
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Nathalie Dinguirard
1Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI USA
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Zachary W. Heimark
1Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI USA
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Nicolas J. Wheeler
1Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI USA
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Jiaye He
2Morgridge Institute for Research, Madison, WI, USA
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Kurt R. Weiss
2Morgridge Institute for Research, Madison, WI, USA
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Nathan E. Schroeder
3Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL USA
4Department of Crop Sciences, University of Illinois at Urbana-Champaign, Urbana, IL USA
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Jan Huisken
2Morgridge Institute for Research, Madison, WI, USA
5Department of Integrative Biology, University of Wisconsin, Madison, WI, USA
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Mostafa Zamanian
1Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI USA
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  • For correspondence: mzamanian@wisc.edu
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ABSTRACT

Lymphatic filariasis (LF) is a chronic debilitating neglected tropical disease (NTD) caused by mosquito-transmitted nematodes that afflicts over 60 million people. Control of LF relies on routine mass drug administration with antiparasitics that clear circulating larval parasites but are ineffective against adults. The development of effective adulticides is hampered by a poor understanding of the processes and tissues driving parasite survival in the host. The adult filariae head region contains essential tissues that control parasite feeding, sensory, secretory, and reproductive behaviors, which express promising molecular substrates for the development of antifilarial drugs, vaccines, and diagnostics. We have adapted spatial transcriptomic approaches to map gene expression patterns across these prioritized but historically intractable head tissues. Spatial and tissue-resolved data reveal distinct biases in the origins of known drug targets and secreted antigens. These data were used to identify potential new drug and vaccine targets, including putative hidden antigens expressed in the alimentary canal, and to spatially associate receptor subunits belonging to druggable families. Spatial transcriptomic approaches provide a powerful resource to aid gene function inference and seed antiparasitic discovery pipelines across helminths of relevance to human and animal health.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/zamanianlab/BmaSpatial-ms

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted August 25, 2021.
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Spatial transcriptomics reveals antiparasitic targets associated with essential behaviors in the human parasite Brugia malayi
Paul M. Airs, Kathy Vaccaro, Kendra J. Gallo, Nathalie Dinguirard, Zachary W. Heimark, Nicolas J. Wheeler, Jiaye He, Kurt R. Weiss, Nathan E. Schroeder, Jan Huisken, Mostafa Zamanian
bioRxiv 2021.08.24.456436; doi: https://doi.org/10.1101/2021.08.24.456436
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Spatial transcriptomics reveals antiparasitic targets associated with essential behaviors in the human parasite Brugia malayi
Paul M. Airs, Kathy Vaccaro, Kendra J. Gallo, Nathalie Dinguirard, Zachary W. Heimark, Nicolas J. Wheeler, Jiaye He, Kurt R. Weiss, Nathan E. Schroeder, Jan Huisken, Mostafa Zamanian
bioRxiv 2021.08.24.456436; doi: https://doi.org/10.1101/2021.08.24.456436

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