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Biological and proteomic studies of Schistosoma mansoni with decreased sensitivity to praziquantel
Affiliation:1. Medical Parasitology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt;2. School of Life Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK;3. Medical Microbiology and Immunology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt;1. Key Laboratory of Animal Parasitology, Ministry of Agriculture of China, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, 200241, China;2. National Institute of Parasitic Diseases, China Center for Disease Control and Prevention, WHO Collaborating Center for Tropical Diseases, Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, 200025, China;1. School of Biological Sciences and Institute for Global Food Security, Queen''s University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, UK;2. School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton, BN2 4GJ, UK;1. Medical Parasitology Department, Kasr Al-Ainy School of Medicine, Cairo University, Egypt;2. Theodor Bilharz Research Institute, Imbaba, Giza, Egypt;3. Medical Parasitology Department, Faculty of Medicine, Helwan University, Cairo, Egypt;4. Pathology Department, Kasr Al-Ainy School of Medicine, Cairo University, Egypt
Abstract:The impact of the laboratory induced Schistosoma mansoni with decreased PZQ sensitivity on the biological performance of its different developmental stages and the concomitant structural changes of adult worms’ total proteins were investigated. PZQ exposed snails showed stoppage of cercarial shedding for eight weeks followed by progressive significant reduction of cercarial production along four successive weeks. In the vertebrate host, in comparison to Schistosoma mansoni susceptible isolate, inoculated cercariae with decreased PZQ sensitivity led to an evident decrease in male to female ratio associated with significant reduction in tissue egg counts and significant increase in dead egg percentage. Significant reduction in the fecundity was also determined. Interestingly, eggs from adult worms with decreased PZQ sensitivity showed two unique features as they found to be smaller and more spherical in addition to the observation of hourglass shaped miracidium in about 10% of the detected mature eggs. Proteomic analysis of adult worms with decreased sensitivity to PZQ using mass spectrometry revealed up-regulation of Ca2+ ATPase 2 and Hsp70. This study can point to the increase incidence of the neuroschistosomiasis due to the small size eggs of Schistosoma mansoni with reduced PZQ sensitivity. These worms can also impact the epidemiology in the field. The study can also provide help to elucidate underlying potential molecular mechanisms of resistance that could lead to possible strategies to reverse drug resistance.
Keywords:Reduced sensitivity  Praziquantel  Hsp70
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