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P. papatasi midgut molecules: gene function and assessing TBV candidates

P. papatasi 中肠分子：基因功能和评估 TBV 候选者

基本信息

批准号：
8070099
负责人：
MARY A MCDOWELL
金额：
$ 2.11万
依托单位：
KANSAS STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-01 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8070099
关键词：
Affect Anabolism Antibodies Binding Binding Proteins Blood Blood coagulation Bolus Infusion Chest Chitinase Code Competence Country Data Development Digestion Diptera Disease Epithelial Cells Epithelium Exhibits Food Galactose Binding Lectin Hematocrit procedure Infection Knowledge Lead Leishmania Leishmania major Leishmaniasis Lutzomyia genus Midgut Molecular Morbidity - disease rate Nature Parasites Patients Peptide Hydrolases Phlebotomus Play Principal Investigator Proteins Prunella vulgaris Psychodidae RNA Interference Research Research Personnel Role Sand Flies Species Specificity Specificity System Testing Thrombin Transcript Trypsin Vaccines Vector-transmitted infectious disease Visceral base chymotrypsin economic impact effective therapy fighting fly gene function glycosylation inhibitor/antagonist insight killings knock-down lipophosphonoglycan mortality novel novel strategies prevent programs receptor skin lesion social transmission process vector vector-based vaccine

项目摘要

DESCRIPTION (provided by applicant): Leishmaniasis, a multi-spectrum disease transmitted by sand fly vectors, has an important social-economic impact in many countries. A strong relationship exists between sand flies and Leishmania such that, in nature, only certain species of sand flies are able to transmit certain species of Leishmania. Such species-specificity is driven by several molecular factors that allow the parasite to infect, survive and multiply within the midgut of the sand fly and be transmitted to a suitable host during a blood meal. Some sand fly species are considered permissive in that they are able to harbor experimental infections of several Leishmania species (e.g. Lutzomyia. longipalpis); other sand fly species are considered restrictive as they can only be infected with the Leishmania species that they carry in nature (e.g. Phlebotomus. papatasi). The precise interactions that lead to this vector competence, whether for permissive or restrictive vectors, remain to be completely elucidated. We previously defined one specific interaction between L. major lipophosphoglycan and a P. papatasi galectin-like molecule that is essential for vector competence and demonstrated that antibodies targeted to this midgut molecule prevent establishment of Leishmania major within the sand fly midgut. Here we propose a set of studies using this restrictive vector/parasite system, to identify additional sand fly molecules that participate in the development of Leishmania within the sand fly midgut. Our studies will specifically focus on the use of RNA interference to assess the roles of proteins such as PpChym2, a blood-induced chymotrypsin that may be involved in early killing of Leishmania; and PpChit1, a midgut-specific chitinase that is thought to play a role in Leishmania escape from the peritrophic matrix. Additionally, recently identified midgut transcripts such as those coding for peritrophins and thrombin-specific inhibitors will also be evaluated. Once identified, P. papatasi molecules that effectively interfere with the development of L. major also will be tested for their broad spectrum activity in other sand fly vector combinations, including P. argentipes and L. donovani. This research will advance the knowledge regarding sand fly-Leishmania interaction and will provide insights for the selection of transmission blocking candidates as a strategy to eliminate and/or reduce leishmaniasis. Project Narrative: Phlebotomine sand flies are the main vectors of leishmaniasis, a multi-spectrum disease that causes substantial morbidity and mortality in the developing world. As effective therapies are un-affordable to most patients and no vaccines are available, vector-based strategies, specifically transmission-blocking vaccines are becoming a choice strategy to control many vector transmitted diseases. Our studies aim at assessing the effect of silencing a selected number of sand fly proteins thought to be involved in Leishmania development within the sand fly; elucidating how these proteins interact with Leishmania parasites undoubtedly will lead to the development of novel strategies to fight parasite transmission.

描述（由申请人提供）：利什曼病是一种由白蛉病媒传播的多谱疾病，在许多国家具有重要的社会经济影响。白蛉和利什曼原虫之间存在很强的关系，因此在自然界中，只有某些种类的白蛉能够传播某些种类的利什曼原虫。这种物种特异性是由几种分子因素驱动的，这些因素使寄生虫能够在白蛉的中肠内感染、生存和繁殖，并在血餐期间传播给合适的宿主。一些白蛉物种被认为是允许的，因为它们能够窝藏几种利什曼原虫物种的实验感染（例如Lutzomyia。longipalpis）;其他白蛉物种被认为是限制性的，因为它们只能被它们在自然界中携带的利什曼原虫物种感染（例如白蛉属（Phlebotomus）。papatasi）。导致这种载体能力的精确相互作用，无论是对于允许性载体还是限制性载体，仍有待完全阐明。我们以前定义了一个特定的相互作用L。主要脂磷酸聚糖和木瓜疟原虫半乳糖凝集素样分子，其对于载体感受态是必需的，并且证明靶向该中肠分子的抗体防止在白蛉中肠内建立主要利什曼原虫。在这里，我们提出了一套研究使用这种限制性载体/寄生虫系统，以确定额外的白蛉分子，参与利什曼原虫的发展内的白蛉中肠。我们的研究将特别关注使用RNA干扰来评估蛋白质的作用，如PpChym 2，一种血液诱导的糜蛋白酶，可能参与利什曼原虫的早期杀死;和PpChit 1，一种中肠特异性几丁质酶，被认为在利什曼原虫逃离围食基质中发挥作用。此外，还将评价最近鉴定的中肠转录物，如编码围肌肽和凝血酶特异性抑制剂的转录物。一旦被鉴定，有效干扰L. papatasi发育的P. papatasi分子。major还将测试它们在其他白蛉媒介组合中的广谱活性，包括银足白蛉和白蛉。donovani。这项研究将推进关于白蛉-利什曼原虫相互作用的知识，并将为选择传播阻断候选者作为消除和/或减少利什曼病的策略提供见解。项目叙述：白蛉是利什曼病的主要媒介，利什曼病是一种多谱疾病，在发展中国家造成大量发病和死亡。由于大多数患者负担不起有效的治疗，并且没有疫苗可用，基于媒介的策略，特别是传播阻断疫苗正在成为控制许多媒介传播疾病的选择策略。我们的研究旨在评估沉默被认为参与利什曼原虫在白蛉体内发育的选定数量的白蛉蛋白质的效果;阐明这些蛋白质如何与利什曼原虫相互作用无疑将导致对抗寄生虫传播的新策略的发展。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A comparative study of fat body morphology in five mosquito species.

五种蚊类脂肪体形态的比较研究。

DOI：
10.1590/s0074-02762011000600015
发表时间：
2011
期刊：
Memorias do Instituto Oswaldo Cruz
影响因子：
2.8
作者：
Martins,GustavoFerreira;Serrão,JoséEduardo;Ramalho-Ortigão,JoséMarcelo;Pimenta,PauloFilemonPaolucci
通讯作者：
Pimenta,PauloFilemonPaolucci

Isolation, primary culture and morphological characterization of oenocytes from Aedes aegypti pupae.

埃及伊蚊蛹卵母细胞的分离、原代培养和形态学特征。

DOI：
10.1016/j.tice.2010.12.003
发表时间：
2011
期刊：
Tissue & cell
影响因子：
2.6
作者：
Martins,GF;Guedes,BAM;Silva,LM;Serrão,JE;Fortes-Dias,CL;Ramalho-Ortigão,JM;Pimenta,PFP
通讯作者：
Pimenta,PFP

Expression plasticity of Phlebotomus papatasi salivary gland genes in distinct ecotopes through the sand fly season.

DOI：
10.1186/1472-6785-11-24
发表时间：
2011-10-10
期刊：
BMC ecology
影响因子：
0
作者：
Coutinho-Abreu IV;Mukbel R;Hanafi HA;Fawaz EY;El-Hossary SS;Wadsworth M;Stayback G;Pitts DA;Abo-Shehada M;Hoel DF;Kamhawi S;Ramalho-Ortigão M;McDowell MA
通讯作者：
McDowell MA

Kazal-type serine proteinase inhibitors in the midgut of Phlebotomus papatasi.