Revisiting the Sequenced Sand Fly Phlebotomus Papatasi Proteome

Leishmaniasis, caused by kinetoplastid parasites of the genus Leishmania, is transmitted by sand flies of the genus Phlebotomus in the Old World. We previously analysed the proteome of Phlebotomus papatasi using a comparative proteogenomic strategy. With the release of P. papatasi and Lutzomyia longipalpis whole genomes in 2023, this provided us a valuable opportunity to reanalyse our mass spectrometry dataset using a genome-informed approach. This current analysis led to the identification of 1,342 high-confidence proteins in P. papatasi, which includes 620 newly identified proteins compared to our previous comparative proteogenomic analysis of P. papatasi. Technical improvements, such as accurate peptide mapping and reduced false positives, enabled deeper proteome coverage. Key enriched categories included cytoskeletal remodelling, vesicle-mediated transport, and immune modulation. Compared to other sand fly datasets, such as that of L. longipalpis, this study represents one of the most comprehensive proteomic resources available for P. papatasi till date. The refined dataset not only enhances our understanding of sand fly biology but also reveals several previously unannotated proteins with predicted roles in secretion and other molecular functions.