Molecular Basis of Infectivity of Brugia malayi microfilariae

马来丝虫感染性的分子基础

• 批准号: 7849184
• 负责人: Michelle Lynn Michalski
• 金额: $ 2.04万
• 依托单位: UNIVERSITY OF WISCONSIN OSHKOSH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-05 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7849184
• 关键词: Adult; Affect; Age; Applications Grants; Arthropod Vectors; Arthropods; Biochemical; Biocompatible Materials; Biological Assay; Biological Process; Blood; Blood Circulation; Boxing; Brugia; Brugia malayi; Candidate Disease Gene; Complementary DNA; Complex; Culicidae; Cytoskeletal Gene; Development; Dirofilariasis; Disease; Drug Delivery Systems; Environment; Female; Filarial Elephantiases; Future; Gene Expression; Genes; Genus Wuchereria; Gerbils; Goals; Grouping; Harvest; Human; Infection; Insecta; Invertebrates; Investigation; Laboratories; Larva; Left; Life; Life Cycle Stages; Lymphatic; Metabolic; Microarray Analysis; Microfilaria; Midgut; Modeling; Molecular; Morbidity - disease rate; Muscle; Nature; Nematoda; Newborn Infant; Ocular Onchocerciasis; Oligonucleotide Microarrays; Onchocerciasis; Parasites; Pattern; Penetration; Peptide Hydrolases; Peripheral; Physiological; Play; Process; Proteins; Proteomics; RNA; Reproduction; Research Personnel; Role; Side; Staging; Surface; Technology; Testing; Time; Transplantation; Vaccine Design; Vaccines; Vertebrates; base; burden of illness; chemotherapeutic agent; disability; filaria; insight; interest; life history; mRNA Expression; man; prevent; protein expression; receptor; research study; transmission process; uptake; vector; vector mosquito; vector transmission

DESCRIPTION (provided by applicant): Lymphatic filariasis is a major cause of morbidity in the tropics, and is caused by mosquito-borne filarial nematodes in the general Wuchereria and Brugia. The life cycle of these nematodes is complex, and relies on transmission of larval stages from mosquito to human, and vice versa. Our long-term objectives are to characterize parasite molecules that are crucial for the infectivity of the L1 stage parasites (microfilariae) for the mosquito host, in the hopes that they can be targeted to curtail man-to-vector transmission. Within the lymphatics of the human host, adult worms copulate and the females shed live immature microfilariae. The larvae are carried into the peripheral circulation and are ingested by the mosquito vector during a blood meal. Newborn microfilariae, however, are not immediately effective for the mosquito host, but must undergo a maturation process in the bloodstream prior to uptake. Maturation is accompanied by changes in microfilarial protein expression, and our hypothesis is that the difference in infectivity between immature and mature microfilariae can be explained by differences in gene expression. We will test this hypothesis by comparing gene expression patterns of immature and mature microfilariae using microarray technology. The specific aims of this project are to: (1) demonstrate the difference in infectivity status of immature and mature Brugia malayi microfilariae using mosquito infectivity assays, (2) use microarray hybridization technology to identify microfilarial genes that are differentially expressed during maturation, and (3) develop candidates for further study by grouping differentially expressed gene products by proposed function and verifying transcriptional patterns using real time PCR. This approach will allow us to identify molecules that promote maturation of newborn B. malayi larvae that allow transmission from man to the disseminating mosquito vector. It's conceivable that parasite molecules that play integral roles in the maturation process can be targeted by drugs or vaccines designed to inhibit reproduction or curtail transmission to the mosquito. These strategies have the potential for breaking the transmission cycle of lymphatic filariasis and reducing the burden of illness and disability in tropical nations.

描述（由申请人提供）：淋巴丝虫病是热带地区发病率的主要原因，是由一般的Wuchereria和Brugia中的蚊子 - 源性丝状线虫引起的。这些线虫的生命周期很复杂，依赖于从蚊子到人类的幼虫阶段的传播，反之亦然。我们的长期目标是表征寄生虫分子，这些分子对于蚊子宿主的L1阶段寄生虫（微丝虫）的感染至关重要，希望它们可以针对降低人类对载体的传播。在人类宿主的淋巴管中，成年蠕虫交配，女性脱落了活的微丝菌。幼虫被带入周围循环中，并在血液粉期间被蚊子摄入。然而，新生儿微乳清菌对蚊子的宿主没有立即有效，但必须在吸收前在血液中进行成熟过程。成熟的伴随着微量流质蛋白表达的变化，我们的假设是，未成熟和成熟的微虫菌之间的感染性差异可以通过基因表达的差异来解释。我们将通过使用微阵列技术比较未成熟和成熟的微丝菌的基因表达模式来检验这一假设。该项目的具体目的是：（1）证明使用蚊子感染性测定法，（2）使用微阵列杂交技术来确定在成熟过程中差异化和（3）实现跨性别的基因，（3）使用微阵列杂交基因来鉴定鉴定基因，（3）使用微阵列杂交基因来识别（3），（3）使用微阵列杂交基因来鉴定（3），（3）使用微阵列杂交基因来鉴定（3），（3）使用跨性别的基因来实现（3），则（3）使用跨性别的基因来实现（3），并且（3）证明了不成熟和成熟的Brugia Malayi微移动性的感染状态差异，并（3）开发了（3），（3）具有（3）的实现，并且（3）具有（3）的实现，（3）具有（3）的实现，（3）具有（3）的实现，（3）时间pcr。 这种方法将使我们能够鉴定出促进新生儿马来语幼虫的成熟的分子，从而使人从人传播到传播蚊子载体。可以想象，在成熟过程中起着不可或缺的作用的寄生虫分子可以通过旨在抑制繁殖或减少向蚊子传播的药物或疫苗来靶向。这些策略具有破坏淋巴丝虫病的传播周期，并减轻热带国家的疾病和残疾负担。

项目成果

A deep sequencing approach to comparatively analyze the transcriptome of lifecycle stages of the filarial worm, Brugia malayi.

• DOI: 10.1371/journal.pntd.0001409
• 发表时间: 2011-12
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Choi YJ;Ghedin E;Berriman M;McQuillan J;Holroyd N;Mayhew GF;Christensen BM;Michalski ML
• 通讯作者: Michalski ML