Malaria parasite evades mosquito immunity by glutaminyl cyclase-mediated posttranslational protein modification.

Autor: Kolli SK; Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., Molina-Cruz A; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852., Araki T; Department of Parasitology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan., Geurten FJA; Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., Ramesar J; Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., Chevalley-Maurel S; Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., Kroeze HJ; Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., Bezemer S; Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., de Korne C; Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.; Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., Withers R; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852., Raytselis N; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852., El Hebieshy AF; Oncode Institute, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands.; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands., Kim RQ; Oncode Institute, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands.; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands., Child MA; Department of Life Sciences, Imperial College London, London, SW7 2AZ, United Kingdom., Kakuta S; Laboratory of Morphology and Image Analysis, Research Support Center, Juntendo University Graduate School of Medicine, Bunkyo, Tokyo 113-8421, Japan., Hisaeda H; Department of Parasitology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan., Kobayashi H; Department of Pathology, National Institute of Infectious Diseases, Shinjukuku, Tokyo 162-8640, Japan., Annoura T; Department of Parasitology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan., Hensbergen PJ; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., Franke-Fayard BM; Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., Barillas-Mury C; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD, 20852., Scheeren FA; Department of Dermatology, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands., Janse CJ; Malaria Research Group, Department of Parasitology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Aug 30; Vol. 119 (35), pp. e2209729119. Date of Electronic Publication: 2022 Aug 22.
DOI: 10.1073/pnas.2209729119
Abstrakt: Glutaminyl cyclase (QC) modifies N-terminal glutamine or glutamic acid residues of target proteins into cyclic pyroglutamic acid (pGlu). Here, we report the biochemical and functional analysis of Plasmodium QC. We show that sporozoites of QC-null mutants of rodent and human malaria parasites are recognized by the mosquito immune system and melanized when they reach the hemocoel. Detailed analyses of rodent malaria QC-null mutants showed that sporozoite numbers in salivary glands are reduced in mosquitoes infected with QC-null or QC catalytically dead mutants. This phenotype can be rescued by genetic complementation or by disrupting mosquito melanization or phagocytosis by hemocytes. Mutation of a single QC-target glutamine of the major sporozoite surface protein (circumsporozoite protein; CSP) of the rodent parasite Plasmodium berghei also results in melanization of sporozoites. These findings indicate that QC-mediated posttranslational modification of surface proteins underlies evasion of killing of sporozoites by the mosquito immune system.
Databáze: MEDLINE