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Plasmodium 6-cysteine proteins determine the commitment of sporozoites to liver-infection
Institution:1. Department of Medical Zoology, Mie University School of Medicine, Mie, Tsu 514-8507, Japan;2. Department of Molecular Protozoology, Research Center for Infectious Disease Control, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan;1. Department of Life Sciences, Natural History Museum, Cromwell Road, London SW7 5BD, UK;2. Queensland Museum, Biodiversity and Geosciences Program, South Brisbane, Queensland 4101, Australia;3. School of Biological Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia;1. Division of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan;2. Parasitology Department, Faculty of Medicine, Benha University, Benha13511, Egypt;3. Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba 278-8530, Japan;4. Department of Sanitary Microbiology, Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-Naka, Kita-Ku, Okayama 700-8530, Japan;5. Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Republic of Korea;6. Department of Parasitology and Tropical Medicine, School of Medicine, Pusan National University, Beomeo-ri, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 626-870, Republic of Korea;1. Laboratory of Veterinary Microbiology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan;2. Laboratory of Veterinary Parasitology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan;3. Beehive Japan Co., Ltd., Tokyo 152-0003, Japan;1. Russian Federal Research Institute of Fisheries and Oceanography, Okruzhnoy Pr. 19, 105187 Moscow, Russia;2. Lomonosov Moscow State University, Leninskiye Gory 1, 119234 Moscow, Russia;3. Moscow representative office of A.O. Kovalevsky Institute of Biology of the Southern Seas of RAS, Leninsky Pr. 38/3, Moscow 119991, Russia
Abstract:Plasmodium sporozoites travel a long way from the site where they are released by a mosquito bite to the liver, where they infect hepatocytes and develop into erythrocyte-invasive forms. The success of this infection depends on the ability of the sporozoites to correctly recognize the hepatocyte as a target and change their behavior from migration to infection. However, how this change is accomplished remains incompletely understood. In this paper, we report that 6-cysteine protein family members expressed in sporozoites including B9 are responsible for this ability. Experiments on parasites using double knockouts of B9 and SPECT2, which is essential for sporozoite to migrate through the hepatocyte, showed that the parasites lacked the capacity to stop migration. This finding suggests that interactions between these parasite proteins and hepatocyte-specific cell surface ligands mediate correct recognition of hepatocytes by sporozoites, which is an essential step in malaria transmission to humans.
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