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Sodalis glossinidius iron acquisition

Sodalis gloseninidius 铁收购

基本信息

批准号：
8231855
负责人：
Laura Jane Runyen-Janecky
金额：
$ 34.41万
依托单位：
UNIVERSITY OF RICHMOND
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2016-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Sodalis glossinidius is a facultative intracellular bacterium that is a secondary symbiont of the tsetse fly, which carries the trypanosome that causes African sleeping sickness. Although the presence of Sodalis within the cells of the tsetse fly has been documented since the mid-1980s, the physiological processes that enable this facultative endosymbiotic bacterium to survive and multiply within the tsetse fly and the intracellular environment are just beginning to be examined. Investigating these processes will contribute to the long-term scientific goals of the PIs research, which are to identify the metabolic and physiological processes that facultative intracellular bacteria employ to survive and/or multiply within their hosts, as well as the elements that regulate gene expression in these environments. The scientific goals of this project are to test hypotheses which address the contribution of putative Sodalis iron acquisition systems to growth of Sodalis within insect cells and the tsetse fly. One system (HemR/HemTUV) is predicted to encode transport proteins that mediate acquisition of heme as an iron source. Heme should be readily available to Sodalis residing in midgut tissue since the tsetse fly blood meal is digested in the midgut to release free heme. The second system is predicted to encode an achromobactin siderophore system that mediates high affinity iron acquisition. This system may be important when Sodalis is within the tsetse fly cells and/or in other environments where free iron is in limiting quantities. In Specific Aims 1 and 2, the ability of the Sodalis heme and achromobactin transporter mutants to grow in tsetse flies and in insect culture will be examined to test hypotheses related to the question of which Sodalis iron acquisition genes are important for growth of Sodalis in these environments. In Specific Aim 3, the function of the putative Sodalis heme and achromobactin transporters will be assessed by analyzing growth of the Sodalis heme and achromobactin transporter mutants in media with either heme or ferri- achromobactin as a sole iron source and by reconstituting the Sodalis systems in heterologous bacterial strains that cannot use heme or achromobactin as iron sources. Studying the tsetse fly-Sodalis symbiosis will have significance to public health. The presence of Sodalis in the tsetse fly may increase tsetse-mediated transmission of the trypanosome, and recent research suggests that paratransgenesis may be a useful control strategy for African trypanosomiasis. For these reasons, a more complete understanding of the nature of the Sodalis-tsetse symbiosis will yield information to help control tsetse-borne disease. PUBLIC HEALTH RELEVANCE: Tsetse-transmitted trypanosomiasis represents a significant global health burden, threatening millions of people in sub-Saharan Africa. Since the presence of Sodalis in the tsetse fly may increase tsetse-mediated transmission of the trypanosome and since recent research suggests that modifying Sodalis glossinidius (one of the bacterial species harbored by the tsetse fly) may be a useful control strategy for African trypanosomiasis, a more complete understanding of the nature of the Sodalis-tsetse symbiosis will yield information to help control tsetse-borne disease. Finally, because Sodalis is one of only a few intracellular insect symbionts to be cultured outside of the host, it can be developed as a model for the study of other intracellular insect symbionts that have an impact on the ability of the insect to transmit disease.

描述（由申请人提供）：Sodalis glossinidius是一种兼性细胞内细菌，是采采蝇的次级共生体，采采蝇携带引起非洲昏睡病的锥虫。虽然自20世纪80年代中期以来，已经记录了采采蝇细胞内Sodalis的存在，但使这种兼性内共生细菌能够在采采蝇和细胞内环境中生存和繁殖的生理过程才刚刚开始被研究。调查这些过程将有助于PI研究的长期科学目标，即确定兼性细胞内细菌在宿主中生存和/或繁殖的代谢和生理过程，以及调节这些环境中基因表达的元素。该项目的科学目标是测试假设，解决假定的Sodalis铁获取系统的贡献，Sodalis在昆虫细胞和采采蝇的生长。一个系统（HemR/HemTUV）预计编码转运蛋白介导收购血红素作为铁源。由于采采蝇血粉在中肠中被消化以释放游离血红素，因此血红素应该容易被驻留在中肠组织中的索达利斯利用。第二个系统被预测为编码一个achromobactin铁载体系统，介导高亲和力铁收购。当Sodalis位于舌蝇细胞内和/或在游离铁含量有限的其他环境中时，该系统可能很重要。在具体目标1和2中，将检查Sodalis血红素和无色菌素转运蛋白突变体在采采蝇和昆虫培养物中生长的能力，以测试与Sodalis铁获取基因对Sodalis在这些环境中的生长很重要的问题相关的假设。在具体目标3中，将通过分析Sodalis血红素和无色菌素转运蛋白突变体在具有血红素或铁-无色菌素作为唯一铁源的培养基中的生长，以及通过在不能使用血红素或无色菌素作为铁源的异源细菌菌株中重构Sodalis系统，来评估推定的Sodalis血红素和无色菌素转运蛋白的功能。研究采采蝇-红腹叶蜂共生关系对公共卫生具有重要意义。采采蝇中Sodalis的存在可能会增加采采蝇介导的锥虫传播，最近的研究表明，parattransgenesis可能是一个有用的控制策略，非洲锥虫。由于这些原因，更全面地了解Sodalis-tsetse共生关系的性质将有助于控制采采蝇传播的疾病。公共卫生相关性：采采蝇传播的锥虫是一个重大的全球健康负担，威胁着撒哈拉以南非洲数百万人。由于在采采蝇中存在Sodalis可能会增加采采蝇介导的锥虫传播，并且由于最近的研究表明，修改Sodalis glossinidius（采采蝇所携带的细菌物种之一）可能是非洲锥虫的一种有用的控制策略，因此更全面地了解Sodalis-采采蝇共生关系的性质将产生有助于控制采采蝇传播疾病的信息。最后，由于Sodalis是在宿主外培养的少数几种细胞内昆虫共生体之一，因此可以将其开发为研究对昆虫传播疾病的能力有影响的其他细胞内昆虫共生体的模型。