Host-pathogen-vector interactions of R. amblyommatis for spotted fever pathogenesis

扁虱是最重要的节肢动物媒介，能够将多种病原体传播到 人类。几个环境和社会学因素对范围和人口有影响 壁虱的扩大，导致美国壁虱传播疾病(Tbd)的数量增加。 最近的扁虱监测研究表明，美洲Amblyomma americanum(孤星扁虱)已迅速 向北扩张，成为当地的硬蜱物种，取代了当地的硬蜱物种 在东北和中西部地区，主要分布在肩部(鹿扁虱)和变形皮(美国狗扁虱)，那里的 观察到病因不明的TBDS患者数量有所增加。美洲斑潜蝇构成一种 公共卫生威胁，因为扁虱表现出非歧视的攻击性咬人行为，并作为媒介 和各种人类病原体的储存库，包括弱立克次体(立克次体病)，埃立克体 查菲和埃文吉氏杆菌(人类埃立克体病)，图拉氏方济氏菌(图拉氏症)，哈特兰病毒(哈特兰) 病毒病)、波本病毒(波本病毒病)和疏螺旋体(南蜱相关皮疹) 疾病)。属于立克次体斑点热群的革兰氏阴性病原菌， 在美国的几个地方经常从美洲曲霉中被鉴定出来。相比之下，目前的 据估计，立克次体(落基山斑点热，RMSF)在变色丝虫中的流行率低于 1%。Amblyommats的高流行率，再加上A.americanum的攻击性咬人行为， 增加了人类感染弱毒葡萄球菌的可能性。在扁虱体内，弱毒乳杆菌展示 在卵巢、中肠和唾液腺等多个器官组织中必需的细胞内生命周期，使 弱毒沙门氏菌对后代和哺乳动物宿主的传播。临床和血清学的几条线 有证据表明，弱小葡萄球菌是RMSF样疾病的病原体。配对血清的分析 从诊断为可能的RMSF的患者中发现，一些患者产生了R。 Amblyommats，但对立克次体不是，证实了Amblyommats可能会引起RMSF样疾病。 人类。对弱毒杆菌具有特异性反应性的患者表现出典型的临床表现 伴有发烧、头痛和肌肉疼痛的轻度RMSF。然而，我们对R的理解存在很大差距。 弱瘤杆菌生物学及其在哺乳动物宿主中引起立克次体病的毒力潜力。基于 可获得的证据：1)严重感染弱肌瘤杆菌的美洲冰草的入侵和扩张 在美国中西部和东北部；2)类似RMSF的病例在 相同的区域；3)本实验室的弱瘤杆菌诱导的细胞病理学实验结果和 发病机制，我们将从最北端的热点之一调查弱瘤杆菌的遗传基础。 对于该物种，在组织培养和动物感染模型中确定毒力潜力，并研究 宿主-病原体-病媒相互作用导致弱毒立克次体病。

Ticks are the most important arthropod vectors capable of transmitting a diverse array of pathogens to humans. Several environmental and sociological factors have contributed to the range and population expansion of ticks, resulting in an increased number of tick-borne diseases (TBDs) in the United States. Recent tick surveillance studies have demonstrated that Amblyomma americanum (lone star tick) has rapidly expanded northward and become the dominant tick species, displacing local tick species such as Ixodes scapularis (deer tick) and Dermacentor variabilis (American dog tick) in the Northeast and Midwest, where the increased number of patients with TBDs of unknown etiology has been observed. A. americanum poses a public health threat as the tick presents non-discriminating aggressive biting behavior and serves as a vector and reservoir for diverse human pathogens, including Rickettsia amblyommatis (rickettsiosis), Ehrlichia chaffeensis and E. ewingii (human ehrlichiosis), Francisella tularensis (tularemia), Heartland virus (Heartland virus disease), Bourbon virus (Bourbon virus disease), and Borrelia lonestari (Southern tick-associated rash illnesses). R. amblyommatis, a Gram-negative pathogen that belongs to the spotted fever group of Rickettsia, has been frequently identified from A. americanum in several parts of the United States. In contrast, the current prevalence of R. rickettsii (Rocky Mountain spotted fever, RMSF) in D. variabilis is estimated to be less than 1%. The high prevalence of R. amblyommatis, combined with the aggressive biting behavior of A. americanum, enhances the probability of human infections with R. amblyommatis. Within ticks, R. amblyommatis exhibits obligatory intracellular lifecycle in multiple organ tissues such as ovaries, midgut, and salivary glands, enabling R. amblyommatis transmission to offspring and mammalian hosts. Several lines of clinical and serological evidence suggest that R. amblyommatis is the etiological agent of RMSF-like illness. Analysis of paired sera from patients diagnosed with probable RMSF revealed that some patients developed antibodies to R. amblyommatis, but not to R. rickettsii, corroborating that R. amblyommatis may cause RMSF-like illnesses in humans. Those patients with specific reactivity to R. amblyommatis presented typical clinical manifestations of a mild RMSF with fever, headache, and myalgia. However, there is a significant gap in our understanding of R. amblyommatis biology and its virulence potential to cause rickettsiosis in mammalian hosts. Based on the available evidence of 1) the invasion and expansion of A. americanum heavily infected with R. amblyommatis in the upper Midwestern and the Northeastern United States; 2) the increasing numbers of RMSF-like cases in the same areas; 3) experimental results from our laboratory for R. amblyommatis-induced cytopathology and pathogenesis, we will investigate the genetic basis of R. amblyommatis from one of the northernmost hotspots for this species, determine the virulence potential in tissue culture and animal infection models, and study the host-pathogen-vector interactions enabling R. amblyommatis rickettsiosis.