Phage Display Screening for Alba Superfamily Proteins from the Human Malaria Parasite, Plasmodium falciparum Reveals a High Level of Association with Protein Modification Pathways and Hints at New Drug Targets

Abstract

Purpose

A 2016 study estimated that over 3 billion people are currently at risk of contracting malaria. Although a wide variety of medications are available to treat malaria, the parasites have started to exhibit resistance to many commonly used therapeutics necessitating a push for new investigations to identify novel drug targets.

Methods

In this study, nucleic acid-binding Alba superfamily proteins of the human malaria parasite, Plasmodium falciparum were investigated to identify interacting protein motifs. A high-throughput molecular screening technique, phage display, coupled with next-generation sequencing was applied to assess large data sets.

Results

Four P. falciparum Alba proteins were used for screening which appear to have distinct roles in parasite biology based on the results of this work. The majority of the peptide motifs identified from phage display were involved in post-translational modification pathways, thus suggesting that parasite-specific gene regulatory mechanisms are involved which could serve as drug targets for novel therapeutics.

Conclusion

This study found 18 peptide motifs which potentially have strong interactions with one or more of the Alba superfamily proteins from P. falciparum. Considering the large fraction of post-translational modification-related peptide motifs identified from this work, one or more of the protein modification pathways could serve as a good target for malaria treatment.

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Fig. 1

Availability of data and materials

The datasets generated during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

I would like to thank Michigan Technological University Research Excellence Fund (R01547) and Portage Health Foundation (R75389). I would also like to thank Dr. Chelsea Nikula (National Physical Laboratory, London UK) for critical reviewing of the manuscript.

Funding

This work was funded by Michigan Technological University Research Excellence Fund (R01547) and Portage Health Foundation (R75389).

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Correspondence to Momoko Tajiri.

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Tajiri, M. Phage Display Screening for Alba Superfamily Proteins from the Human Malaria Parasite, Plasmodium falciparum Reveals a High Level of Association with Protein Modification Pathways and Hints at New Drug Targets. Acta Parasit. (2021). https://doi.org/10.1007/s11686-021-00339-x

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Keywords

  • Phage display
  • Next-generation sequencing
  • Plasmodium falciparum
  • Alba superfamily proteins