Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
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Malaria is one of the most important infectious diseases in the world, and it has many economic and social impacts on populations, especially in poor countries. Transmission-blocking vaccines (TBVs) are valuable tools for malaria eradication. A study on Anopheles gambiae revealed that polyclonal antibodies to carboxypeptidase B1 of A. gambiae can block sexual parasite development in the mosquito midgut. Hence, it was introduced as a TBV target in regions where A. gambiae is the main malaria vector. However, in Iran and neighboring countries as far as China, the main malaria vector is Anopheles stephensi. Also, the genome of this organism has not been sequenced yet. Therefore, in this study, carboxypeptidase B1 of A. stephensi was characterized by genomic and proteomic approaches. Furthermore, its expression pattern after ingestion of Plasmodium falciparum gametocytes and the effect of anti-CPBAs1 antibodies on sexual parasite development were evaluated. Our results revealed that the cpbAs1 expression level was increased after ingestion of the mature gametocytes of P. falciparum and that anti-CPBAs1 directed antibodies could significantly reduce the mosquito infection rate in the test group compared with the control group. Therefore, according to our findings and with respect to the high similarity of carboxypeptidase enzymes between the two main malaria vectors in Africa (A. gambiae) and Asia (A. stephensi) and the presence of other sympatric vectors, CPBAs1 could be introduced as a TBV candidate in regions where A. stephensi is the main malaria vector, and this will broaden the scope for the potential wider application of CPBAs1 antigen homologs/orthologs.
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PMID:Molecular characterization of the carboxypeptidase B1 of Anopheles stephensi and its evaluation as a target for transmission-blocking vaccines. 2356 11

Malaria is a vector-borne infectious disease that is considered a priority of the World Health Organization due to its enormous impacts on global health. Plasmodium spp. (Haemosporida: Plasmodiidae), Anopheles spp. (Diptera: Culicidae), and a suitable host are the key elements for malaria transmission. To disrupt the parasitic life cycle of malaria or prevent its transmission, these three key elements should be targeted by effective control strategies. Development of vaccines that interrupt malaria transmission is one of the solutions that has been recommended to the countries that aim to eliminate malaria. With respect to the important role of Anopheles stephensi in malaria transmission and involvement of Anopheles carboxypeptidase B1 in sexual parasite development, we characterized the second member of cpb gene family (cpbAs2) of An. Stephensi to provide some basic information and evaluate significance of cpbAs2's role in complementing sexual plasmodium development role of cpbAs1. The cpbAs2 mRNA sequence was characterized by 3' and 5' RACE and the structural features of its coded protein were studied by in silico modeling. The coding sequence and gene structure of cpbAs2 were determined empirically and compared with the in silico predictions from the An. stephensi genome sequencing project. Furthermore, homology modeling revealed that its structure is very similar to the structurally important domains of procarboxypeptidase B2 in humans. This study provides basic molecular and structural information about another member of the cpb gene family of An. stephensi. The reported results are informative and necessary for evaluation of the role of this gene in sexual parasite development by future studies.
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PMID:Identification, Molecular Characterization, and In Silico Structural Analysis of Carboxypeptidase B2 of Anopheles stephensi. 3012 10