Biology ETDs

Publication Date

Spring 5-12-2018

Abstract

Schistosomiasis, caused by trematodes in the genus Schistosoma, is a widespread neglected tropical disease with the species S. mansoni infecting over 100 million people. We aimed to better understand the snail host and parasite responses during intramolluscan stages of infection by performing dual RNA-Seq on field-collected snails with natural infections from western Kenya. We collected uninfected Biomphalaria pfeifferi, B. pfeifferi with a patent cercariae-producing S. mansoni infection, and B. pfeifferi exposed to field-collected S. mansoni at 1 and 3d (days post infection).

We first created a high-quality B. pfeifferi transcriptome to identify the snail response to S. mansoni infection. As reported in Chapter 2 and published in PLoS NTD, B. pfeifferi individuals show different patterns of transcriptional response, indicating that the ability of field-derived snails to support and respond to infection is variable. Alterations in transcripts associated with reproduction were noted, including for oviposition-related hormones and enzymes involved in metabolism of bioactive monoamines. Both generalized stress and immune factors immune factors exhibited complex transcriptional responses.

Chapter 3 explores S. mansoni transcriptomic activity during intramolluscan stages. The core metabolic transcriptome includes transporters required for glucose, amino acid, and nucleoside acquisition from B. pfeifferi. Proteases were expressed at all stages including elastases. Transcripts associated with GPCRs, and stress and defense responses were well represented. We noted transcripts homologous to planarian anti-bacterial factors, neuropeptides and receptors associated with schistosome germinal cell maintenance that could also impact host reproduction. The presence of another trematode species (amphistome) in one snail was associated with repressed S. mansoni transcriptional activity.

Chapter 4 looks at the combined responses of the snail and parasite to the molluscicide, niclosamide. The parasite maintains expression of >80% of transcripts expressed in shedding stages with little evidence of a lethal effect from niclosamide. Conversely, niclosamide provokes a dramatic response in B. pfeifferi, with a majority of features up-regulated, including those for xenobiotic processing. The response of B. pfeifferi to both niclosamide and patent S. mansoni infection was greater than to either stressor alone with evidence of apoptosis, reduced protein synthesis, reduced production of detoxification enzymes, and diminished innate immune function.

Keywords

dual RNA-Seq, neglected tropical diseases, de novo transcriptomics, host-parasite interactions, symbionts

Document Type

Dissertation

Degree Name

Biology

Level of Degree

Doctoral

Department Name

UNM Biology Department

First Committee Member (Chair)

Dr. Eric S Loker

Second Committee Member

Dr. Christina Takacs-Vesbach

Third Committee Member

Dr. Ben Hanelt

Fourth Committee Member

Dr. Tim Yoshino

Download

Share

COinS