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PreprintCC BYbioRxiv

Multi-omic profiling of Plasmodium knowlesi blood stages identifies host adaptation barriers

  1. 1School of Biological Sciences, Nanyang Technological University, Singapore

Abstract

The zoonotic parasite Plasmodium knowlesi has emerged as a widespread cause of human malaria in Southeast Asia. We assembled a high-resolution transcriptome of zoonotic P. knowlesi across its intraerythrocytic developmental cycle and combined transcriptomics, quantitative proteomics and thermal stability measurements to compare parasites cultured in macaque and human red blood cells. We found that P. knowlesi accelerates through the ring stage to settle at the same developmental pace as P. falciparum during the trophozoite and schizont stages. Subsequent multi-omic analysis revealed broad transcriptional and proteomic adaptations of P. knowlesi to the human host cell environment. Parasites cultured in human cells expressed glutathione synthetase earlier and displayed changes in upstream processes that include NADPH production by the pentose phosphate pathway and glutamine synthesis. These changes were accompanied by further differences in the expression of ribosomal subunits and mitochondrial respiratory complexes. Together, our findings offer a systems-level view of non-genetic adaptations of P. knowlesi to the human red blood cell environment.

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BibTeX
@misc{pazicky2026multiomic,
  title = {{Multi-omic profiling of Plasmodium knowlesi blood stages identifies host adaptation barriers}},
  author = {S. Pazicky and N. Aranciaga and X. Gao and A. Wen and K. Rukruam and S. Tjia and H. Duong and K. D. Go and P. Bifani and M. Kucharski and P. R. Preiser and Z. Bozdech},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.02.756168},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.02.756168v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Multi-omic profiling of Plasmodium knowlesi blood stages identifies host adaptation barriers
AU  - S. Pazicky
AU  - N. Aranciaga
AU  - X. Gao
AU  - A. Wen
AU  - K. Rukruam
AU  - S. Tjia
AU  - H. Duong
AU  - K. D. Go
AU  - P. Bifani
AU  - M. Kucharski
AU  - P. R. Preiser
AU  - Z. Bozdech
PY  - 2026
DA  - 2026/10/02
PB  - bioRxiv
DO  - 10.64898/2026.10.02.756168
UR  - https://www.biorxiv.org/content/10.64898/2026.10.02.756168v1
AB  - The zoonotic parasite Plasmodium knowlesi has emerged as a widespread cause of human malaria in Southeast Asia. We assembled a high-resolution transcriptome of zoonotic P. knowlesi across its intraerythrocytic developmental cycle and combined transcriptomics, quantitative proteomics and thermal stability measurements to compare parasites cultured in macaque and human red blood cells. We found that P. knowlesi accelerates through the ring stage to settle at the same developmental pace as P. falciparum during the trophozoite and schizont stages. Subsequent multi-omic analysis revealed broad transcriptional and proteomic adaptations of P. knowlesi to the human host cell environment. Parasites cultured in human cells expressed glutathione synthetase earlier and displayed changes in upstream processes that include NADPH production by the pentose phosphate pathway and glutamine synthesis. These changes were accompanied by further differences in the expression of ribosomal subunits and mitochondrial respiratory complexes. Together, our findings offer a systems-level view of non-genetic adaptations of P. knowlesi to the human red blood cell environment.
ER  -