Emerging Flea-Borne Rickettsial Diseases: vector competence and transmission biology

新出现的跳蚤传播立克次体病：媒介能力和传播生物学

• 批准号: 10674916
• 负责人: Kevin R. Macaluso
• 金额: $ 45.93万
• 依托单位: UNIVERSITY OF SOUTH ALABAMA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674916
• 关键词: Address; Affect; Africa; Africa South of the Sahara; Antigens; Area; Arthropod Vectors; Arthropods; Asia; Biological; Biological Assay; Biology; Blood; California; Characteristics; Complex; Culicidae; Data; Disease; Disease Management; Disease Outbreaks; Ecosystem; Environment; Epidemiology; Europe; Experimental Designs; Felis catus; Fever; Fleas; Funding; Genes; Genome; Genotype; Genus Felis; Goals; Health; Horizontal Disease Transmission; Human; Immune; Immune response; Infection; Insecta; Intervention; Investigation; Knowledge; Mechanics; Mediating; Modeling; Molecular; North America; Oceania; Organism; Pathogenicity; Population; Publishing; Recording of previous events; Regulation; Reporting; Reproducibility; Research; Resources; Rickettsia; Rickettsia Infections; Rickettsia felis; Rickettsia typhi; Role; Salivary; Skin; South America; System; Techniques; Testing; Texas; Ticks; Typhus; United States; Vector-transmitted infectious disease; co-infection; comparative; experience; experimental study; feeding; flea-borne; human pathogen; innovation; member; novel; novel strategies; pathogen; pathogenic bacteria; prevent; response; spotted fever; suburb; transmission process; vector; vector competence; vector transmission

Rickettsia felis was originally identified in the United States as a human pathogen in 1991 and is now associated with human infection in North and South America, Europe, Africa, Asia, and Oceania. Our ultimate goal for this research is to elucidate the biological and molecular mechanisms that are critical to rickettsial transmission by fleas in order to better understand the epidemiology of flea-borne rickettsial diseases and identify novel points of intervention. Recent discoveries including transmission of R. felis in the absence of a rickettsemic host and the identification of multiple flea-borne rickettsial agents cocirculating in flea populations have guided the research to determine if sympatric rickettsial agents circulating in flea populations influence the transmission one another. Additionally, the assembly of the cat flea genome now allows for investigation of the flea-derived factors that facilitate or prevent Rickettsia transmission. The experimental focus of this proposal is to delineate horizontal transmission mechanisms through comparative analyses of coinfections using three distinct rickettsial strains in cat flea transmission bioassays. The flea-derived molecules associated with the transmission of Rickettsia by flea hosts are not known. Studies will also employ gene-editing in fleas to identify transmission determinants in a flea transmission system. Two limiting factors for vector/disease management and the barriers to advancing the field are the scant knowledge of 1) basic transmission biology of R. felis and other rickettsial pathogens in the context of coinfections and, 2) the flea-derived determinants of transmission. The need to overcome these barriers is evident as field collected fleas in areas of flea-borne rickettsioses outbreaks have multiple rickettsial agents circulating in the vector population and the fleas are known to be vectors of a number of pathogens, thus providing knowledge with a broad impact. Through completion of the specific aims outlined in this proposal, these studies will overcome the hurdles by delineating the role of coinfections in the transmission of R. felis (Specific Aim 1) and through identification of flea-derived molecules regulated in response to rickettsial infection relates to vector competence (Specific Aim 2). Thus, this is a multifaceted approach to decipher the vector and pathogen-associated factors essential to transmission and will provide a platform to examine other flea-borne bacterial pathogens.

猫立克次体最初于1991年在美国被确定为人类病原体，现在已被 在北美洲和南美洲、欧洲、非洲、亚洲和大洋洲，与人类感染有关。我们 这项研究的最终目标是阐明生物和分子机制，这是至关重要的， 通过跳蚤传播立克次体，以便更好地了解跳蚤传播立克次体的流行病学 疾病和确定新的干预点。最近的发现包括R.猫在 缺乏立克次体宿主和鉴定出多种蚤传播立克次体因子 在跳蚤种群中的共循环引导了研究，以确定同域立克次体因子是否 在跳蚤种群中循环影响彼此的传播。此外， 猫蚤基因组现在允许研究促进或预防立克次体的蚤源因子 传输这项建议的实验重点是描绘水平传输机制 通过比较分析猫蚤传播中使用三种不同立克次体菌株的合并感染， 生物测定与通过跳蚤宿主传播立克次体相关的跳蚤衍生分子不是 知道的研究还将利用跳蚤中的基因编辑来确定跳蚤中的传播决定因素 传输系统病媒/疾病管理的两个限制因素和前进的障碍 该领域的知识是：1）基本的传播生物学的R。猫和其他立克次体 病原体在合并感染的情况下，2）跳蚤衍生的传播决定因素。需要 克服这些障碍是显而易见的， 有多种立克次体因子在媒介种群中循环，并且已知跳蚤是媒介 许多病原体的研究，从而提供具有广泛影响的知识。通过完成 这些研究将克服障碍，界定以下方面的作用： 在传播R.猫（具体目标1），并通过识别跳蚤衍生 在立克次体感染应答中调节的分子与载体感受态有关（特异性目标2）。 因此，这是一个多方面的方法来破译载体和病原体相关的因素至关重要， 传播，并将提供一个平台，以检查其他跳蚤传播的细菌病原体。

项目成果

Rickettsia felis: A Review of Transmission Mechanisms of an Emerging Pathogen.

• DOI: 10.3390/tropicalmed2040064
• 发表时间: 2017-12-19
• 期刊: Tropical medicine and infectious disease
• 影响因子: 2.9
• 作者: Legendre KP;Macaluso KR
• 通讯作者: Macaluso KR

Rickettsia felis, an Emerging Flea-Borne Rickettsiosis.

• DOI: 10.1007/s40475-016-0070-6
• 发表时间: 2016
• 期刊: Current tropical medicine reports
• 影响因子: 5.4
• 作者: Brown LD;Macaluso KR
• 通讯作者: Macaluso KR

Unpacking the intricacies of Rickettsia-vector interactions.

• DOI: 10.1016/j.pt.2021.05.008
• 发表时间: 2021-08
• 期刊: Trends in parasitology
• 影响因子: 9.6
• 作者: Laukaitis HJ;Macaluso KR
• 通讯作者: Macaluso KR

Effect of Rickettsia felis Strain Variation on Infection, Transmission, and Fitness in the Cat Flea (Siphonaptera: Pulicidae).

猫立克次体菌株变异对猫蚤（Siphonaptera：Pulicidae）感染、传播和适应性的影响。

• DOI: 10.1093/jme/tjx046
• 发表时间: 2017
• 期刊: Journal of medical entomology
• 影响因子: 2.1
• 作者: Healy,SeanP;Brown,LisaD;Hagstrom,MelenaR;Foil,LaneD;Macaluso,KevinR
• 通讯作者: Macaluso,KevinR

Revisiting the sialome of the cat flea Ctenocephalides felis.

• DOI: 10.1371/journal.pone.0279070
• 发表时间: 2023
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Lu, Stephen;Danchenko, Monika;Macaluso, Kevin R.;Ribeiro, Jose M. C.
• 通讯作者: Ribeiro, Jose M. C.