Characterization of a Sulfhydryl Oxidase From Plasmodium berghei as a Target for Blocking Parasite Transmission
Quiescin sulfhydryl oxidase (QSOX), present in a wide variety of eukaryotic species, catalyzes the insertion of disulfide bonds into unfolded, reduced proteins. Here we characterized the QSOX protein from the rodent malaria parasite Plasmodium berghei (PbQSOX), which is conserved in all sequenced ma...
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| Format: | Article |
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Frontiers Media S.A.
2020-06-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2020.00311/full |
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| author | Wenqi Zheng Wenqi Zheng Fei Liu Feng Du Fan Yang Xu Kou Xu Kou Yiwen He Hui Feng Qi Fan Enjie Luo Hui Min Hui Min Jun Miao Liwang Cui Yaming Cao |
| author_facet | Wenqi Zheng Wenqi Zheng Fei Liu Feng Du Fan Yang Xu Kou Xu Kou Yiwen He Hui Feng Qi Fan Enjie Luo Hui Min Hui Min Jun Miao Liwang Cui Yaming Cao |
| author_sort | Wenqi Zheng |
| collection | DOAJ |
| description | Quiescin sulfhydryl oxidase (QSOX), present in a wide variety of eukaryotic species, catalyzes the insertion of disulfide bonds into unfolded, reduced proteins. Here we characterized the QSOX protein from the rodent malaria parasite Plasmodium berghei (PbQSOX), which is conserved in all sequenced malaria parasite species. The PbQSOX protein was not expressed in asexual erythrocytic stages, but was most abundantly expressed in ookinetes. Indirect immunofluorescence assays revealed PbQSOX was not only localized in cytoplasm of gametocytes, gametes and ookinetes, but also expressed on the surface of gametes and ookinetes. Western blot identified extracellular presence of PbQSOX in the culture medium of ookinetes suggestive of secretion. Pbqsox deletion (Δpbqsox) did not affect asexual intraerythrocytic development, but reduced exflagellation of male gametocytes as well as formation and maturation of ookinetes. Pbqsox deletion also led to a significant increase in the reduced thiol groups of ookinete surface proteins, suggesting that it may play a role in maintaining the integrity of disulfide bonds of surface proteins, which might be needed for ookinete development. Mosquitoes that fed on Δpbqsox-infected mice showed a significant reduction in ookinete and oocyst numbers compared to those fed on wild-type parasite-infected mice. Further, both polyclonal mouse antisera and a monoclonal antibody against the recombinant PbQSOX exhibited substantial transmission-blocking activities in in vitro and mosquito feeding assays, suggesting QSOX is a potential target for blocking parasite transmission. |
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| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-13T06:12:25Z |
| publishDate | 2020-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-9a771c6fadfc4e9ab79ca36bc7bbb44f2022-12-21T23:57:03ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-06-011010.3389/fcimb.2020.00311549674Characterization of a Sulfhydryl Oxidase From Plasmodium berghei as a Target for Blocking Parasite TransmissionWenqi Zheng0Wenqi Zheng1Fei Liu2Feng Du3Fan Yang4Xu Kou5Xu Kou6Yiwen He7Hui Feng8Qi Fan9Enjie Luo10Hui Min11Hui Min12Jun Miao13Liwang Cui14Yaming Cao15Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Clinical Laboratory, Affiliated Hospital of Inner Mongolian Medical University, Hohhot, ChinaDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Animal Quarantine, College of Animal Husbandry and Veterinary Sciences, Liaoning Medical University, Jinzhou, ChinaDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDalian Institute of Biotechnology, Dalian, ChinaDepartment of Pathogen Biology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaDepartment of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesDepartment of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesDepartment of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesDepartment of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, ChinaQuiescin sulfhydryl oxidase (QSOX), present in a wide variety of eukaryotic species, catalyzes the insertion of disulfide bonds into unfolded, reduced proteins. Here we characterized the QSOX protein from the rodent malaria parasite Plasmodium berghei (PbQSOX), which is conserved in all sequenced malaria parasite species. The PbQSOX protein was not expressed in asexual erythrocytic stages, but was most abundantly expressed in ookinetes. Indirect immunofluorescence assays revealed PbQSOX was not only localized in cytoplasm of gametocytes, gametes and ookinetes, but also expressed on the surface of gametes and ookinetes. Western blot identified extracellular presence of PbQSOX in the culture medium of ookinetes suggestive of secretion. Pbqsox deletion (Δpbqsox) did not affect asexual intraerythrocytic development, but reduced exflagellation of male gametocytes as well as formation and maturation of ookinetes. Pbqsox deletion also led to a significant increase in the reduced thiol groups of ookinete surface proteins, suggesting that it may play a role in maintaining the integrity of disulfide bonds of surface proteins, which might be needed for ookinete development. Mosquitoes that fed on Δpbqsox-infected mice showed a significant reduction in ookinete and oocyst numbers compared to those fed on wild-type parasite-infected mice. Further, both polyclonal mouse antisera and a monoclonal antibody against the recombinant PbQSOX exhibited substantial transmission-blocking activities in in vitro and mosquito feeding assays, suggesting QSOX is a potential target for blocking parasite transmission.https://www.frontiersin.org/article/10.3389/fcimb.2020.00311/fullmalariaPlasmodium bergheiquiescin sulfhydryl oxidasesexual developmenttransmission-blocking vaccine |
| spellingShingle | Wenqi Zheng Wenqi Zheng Fei Liu Feng Du Fan Yang Xu Kou Xu Kou Yiwen He Hui Feng Qi Fan Enjie Luo Hui Min Hui Min Jun Miao Liwang Cui Yaming Cao Characterization of a Sulfhydryl Oxidase From Plasmodium berghei as a Target for Blocking Parasite Transmission Frontiers in Cellular and Infection Microbiology malaria Plasmodium berghei quiescin sulfhydryl oxidase sexual development transmission-blocking vaccine |
| title | Characterization of a Sulfhydryl Oxidase From Plasmodium berghei as a Target for Blocking Parasite Transmission |
| title_full | Characterization of a Sulfhydryl Oxidase From Plasmodium berghei as a Target for Blocking Parasite Transmission |
| title_fullStr | Characterization of a Sulfhydryl Oxidase From Plasmodium berghei as a Target for Blocking Parasite Transmission |
| title_full_unstemmed | Characterization of a Sulfhydryl Oxidase From Plasmodium berghei as a Target for Blocking Parasite Transmission |
| title_short | Characterization of a Sulfhydryl Oxidase From Plasmodium berghei as a Target for Blocking Parasite Transmission |
| title_sort | characterization of a sulfhydryl oxidase from plasmodium berghei as a target for blocking parasite transmission |
| topic | malaria Plasmodium berghei quiescin sulfhydryl oxidase sexual development transmission-blocking vaccine |
| url | https://www.frontiersin.org/article/10.3389/fcimb.2020.00311/full |
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