Evaluation of Plasmodium falciparum PSSP17 essentiality in human-to-mosquito transmission and its prospective candidacy as a biomarker

B López-Gutiérrez; N Hathaway; L Alonso-Palomares; V O Nyasembe; M Kato; T Hamerly; J B Parr; J J Juliano; M Harbers; R R Dinglasan

doi:10.1016/j.isci.2025.113919

Evaluation of Plasmodium falciparum PSSP17 essentiality in human-to-mosquito transmission and its prospective candidacy as a biomarker

iScience. 2025 Oct 31;28(12):113919. doi: 10.1016/j.isci.2025.113919. eCollection 2025 Dec 19.

Authors

B López-Gutiérrez¹, N Hathaway², L Alonso-Palomares¹, V O Nyasembe¹, M Kato³, T Hamerly¹, J B Parr^{4

5}, J J Juliano^{4

5

6}, M Harbers⁷, R R Dinglasan¹

Affiliations

¹ Department of Infectious Diseases & Immunology & Emerging Pathogens Institute, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
² Department of Genomics and Computational Biology, University of Massachusetts Chan School of Medicine, Worchester, MA, USA.
³ Frontier Institute Co. Ltd., Ishikari, Japan.
⁴ Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁶ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁷ CellFree Sciences Co. Ltd., Yokohama, Japan.

Abstract

Reliance on detecting the Plasmodium falciparum histidine-rich protein 2 (PfHRP2) biomarker by current rapid diagnostic tests (RDTs) is compromised by the emergence of pfhrp2/3 deletion strains that evade detection and treatment. Additional biomarkers can arguably expand the diagnostic toolbox, but these new biomarkers must be essential for parasite development to avoid similar outcomes to PfHRP2. Recently, Plasmodium sexual stage protein 17 (PSSP17; PF3D7_1218800) was identified in saliva from children with subclinical infections, offering a non-invasive modality for malaria diagnosis. However, the essentiality of PSSP17 has not been determined. We show that pssp17 is dispensable in P. falciparum asexual stages but is important for onward transmission by mosquitoes. Importantly, the 19,280 publicly available P. falciparum genomes did not reveal naturally occurring deletions. Thus, should Δpssp17 mutants arise, mosquitoes cannot effectively transmit them. These data suggest that the further consideration of PSSP17 as an RDT biomarker for non-invasive, saliva-based sensitive RDTs is warranted.

Keywords: Diagnostics; Genetics; Parasitology.