Transcriptome and histone epigenome of Plasmodium vivax salivary-gland sporozoites point to tight regulatory control and mechanisms for liver-stage differentiation in relapsing malaria

Muller I, Jex AR, Kappe SH, Mikolajczak SA, Sattabongkot J, Patrapuvich R, Lindner S, Flannery EL, Koepfli C, Ansell B, Lerch A, Emery-Corbin SJ, Charnaud S, Smith J, Merrienne N, Swearingen KE, Moritz RL, Petter M, Duffy MF, Chuenchob V (2019)

Publication Type: Journal article

Publication year: 2019

Journal

International Journal For Parasitology Elsevier

DOI: 10.1016/j.ijpara.2019.02.007

Abstract

Plasmodium vivax is the key obstacle to malaria elimination in Asia and Latin America, largely attributed to its ability to form resilient hypnozoites (sleeper cells) in the host liver that escape treatment and cause relapsing infections. The decision to form hypnozoites is made early in the liver infection and may already be set in sporozoites prior to invasion. To better understand these early stages of infection, we undertook a comprehensive transcriptomic and histone epigenetic characterization of P. vivax sporozoites. Through comparisons with recently published proteomic data for the P. vivax sporozoite, our study found that although highly transcribed, transcripts associated with functions needed for early infection of the vertebrate host are not detectable as proteins and may be regulated through translational repression. We identified differential transcription between the sporozoite and published transcriptomes of asexual blood stages and mixed versus hypnozoite-enriched liver stages. These comparisons point to multiple layers of transcriptional, post-transcriptional and post-translational control that appear active in sporozoites and to a lesser extent hypnozoites, but are largely absent in replicating liver schizonts or mixed blood stages. We also characterised histone epigenetic modifications in the P. vivax sporozoite and explored their role in regulating transcription. Collectively, these data support the hypothesis that the sporozoite is a tightly programmed stage to infect the human host and identify mechanisms for hypnozoite formation that may be further explored in liver stage models.

Authors with CRIS profile

Michaela Petter Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene

Involved external institutions

Institute for Systems Biology US United States (USA) (US) Seattle Children's Hospital US United States (USA) (US) Mahidol University / มหาวิทยาลัยมหิดล TH Thailand (TH) Walter and Eliza Hall Institute of Medical Research (WEHI) AU Australia (AU) Institut Pasteur FR France (FR) The University of Melbourne AU Australia (AU) Pennsylvania State University (Penn State) US United States (USA) (US) University of Washington US United States (USA) (US)

How to cite

APA:

Muller, I., Jex, A.R., Kappe, S.H., Mikolajczak, S.A., Sattabongkot, J., Patrapuvich, R.,... Chuenchob, V. (2019). Transcriptome and histone epigenome of Plasmodium vivax salivary-gland sporozoites point to tight regulatory control and mechanisms for liver-stage differentiation in relapsing malaria. International Journal For Parasitology. https://dx.doi.org/10.1016/j.ijpara.2019.02.007

MLA:

Muller, Ivo, et al. "Transcriptome and histone epigenome of Plasmodium vivax salivary-gland sporozoites point to tight regulatory control and mechanisms for liver-stage differentiation in relapsing malaria." International Journal For Parasitology (2019).

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