Development of a novel multipurpose model to propagate and study the tick transmission cycle of relapsing fever spirochetes from Eurasia.

开发一种新型多用途模型，用于繁殖和研究欧亚大陆回归热螺旋体的蜱传播周期。

• 批准号: 10651550
• 负责人: Job E Lopez
• 金额: $ 20.06万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-05 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10651550
• 关键词: Address; Asia; Bacteria; Bacterial Genome; Blood; Borrelia; Child; Chromosomes; Climate; Comparative Genomic Analysis; Complex; Country; Data; Development; Disease; Gene Rearrangement; Genes; Genetic Recombination; Genome; Genome Stability; Genomics; Goals; Growth; Health; In Vitro; Knowledge; Life Cycle Stages; Literature; Longevity; Maintenance; Mammals; Middle East; Modeling; Molecular; Molecular Probes; Morbidity - disease rate; Natural Source; Order Spirochaetales; Ornithodoros; Pathogenesis; Phylogenetic Analysis; Plasmids; Politics; Positioning Attribute; Public Health; Publications; Publishing; Relapsing Fever; Replicon; Reporting; Research; Resource-limited setting; Resources; Southern Blotting; System; Testing; Ticks; Time; Ukraine; chicken egg; cost effective; egg; epidemiology study; genome annotation; genome resource; genomic tools; improved; low income country; model development; mortality; neglect; novel; pathogen; pathogen genomics; poor communities; relapsing fever borrelia; tick bite; tick transmission; transmission process; vector; vector competence; vector tick; vector-borne pathogen

Project Summary Relapsing fever (RF) spirochetes are a group of neglected vector-borne pathogens that are a significant cause of child morbidity and mortality. The current approaches to grow and assess tick transmission of RF spirochetes are impractical in resource limited settings where they are prevalent. For example, propagating spirochetes in culture medium is expensive and labor intensive. Moreover, prolonged in vitro propagation in medium causes DNA rearrangements of their already exceedingly complex genomes, and this results in diminished vector colonization and pathogenesis. There is a critical need for cost effective practical approaches to grow and study RF spirochetes from neglected regions of the globe. This project builds on our prior our publication reporting the first isolation of Borrelia caucasica, which is part of the Persica species complex and is distributed through Eurasia and the Middle East. Moreover, our recent advances RF spirochete genomics addressed a major limitation in the field and resulted in complete chromosome and plasmid assembled and annotated genomes. The genomics tools we developed can now be utilized to characterize a model for the Persica complex species. Interestingly, historical literature suggested that embryonated chicken eggs (ECEs) could be infected with RF spirochetes by tick bite and the bacteria grew in this system. However, at the time molecular and genomics resources were not available to characterize this model and knowledge gaps remain about the pathogens genomic stability in ECEs. Leveraging recent advances in RF spirochete genomics, the ECE model can now be fully developed to study Persica complex species. In this study, two aims are proposed. The first aim is to utilize genomics resources for RF spirochetes and evaluate plasmid diversity and identify unique plasmid markers of B. caucasica isolates through a comparative genomic analysis. The first objective is to complete reference quality genomes assemblies of B. caucasica isolates and perform a comparative genomics analysis to identify plasmid markers. The second objective is to develop a panel of specific probes needed to evaluate plasmid retention and rearrangements during the B. caucasica life cycle. In the second aim, we will assess genomic changes of B. caucasica using the tick – ECE model. The first objective is to develop the B. caucasica model in ECEs and evaluate spirochete growth, tick acquisition, and subsequent tick transmission of spirochetes to naïve eggs. The second objective is to assess plasmid stability and the ability of B. caucasica to remain infectious after passage through ECEs. The establishment of the ECE model will result in a cost-effective approach to amplify RF spirochetes in the absence of culture medium. Moreover, the development of this model offers a practical system to study the transmission cycle and vector competence of RF spirochetes in resource limited settings. With the emergence and health burden of RF spirochetes in low-income countries, it is important to develop systems to propagate and study these neglected pathogens.

项目总结