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

Reliance on detecting the <i>Plasmodium falciparum</i> histidine-rich protein 2 (PfHRP2) biomarker by current rapid diagnostic tests (RDTs) is compromised by the emergence of <i>pfhrp2/3</i> 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, <i>Plasmodium</i> 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 <i>pssp17</i> is dispensable in <i>P. falciparum</i> asexual stages but is important for onward transmission by mosquitoes. Importantly, the 19,280 publicly available <i>P. falciparum</i> genomes did not reveal naturally occurring deletions. Thus, should Δ<i>pssp17</i> 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.