Stone Nathan E, Hamond Camila, Clegg Joel R, McDonough Ryelan F, Bourgeois Reanna M, Ballard Rebecca, Thornton Natalie B, Nuttall Marianece, Hertzel Hannah, Anderson Tammy, Whealy Ryann N, Timm Skylar, Roberts Alexander K, Barragán Verónica, Phipatanakul Wanda, Leibler Jessica H, Benson Hayley, Specht Aubrey, White Ruairi, LeCount Karen, Furstenau Tara N, Galloway Renee L, Hill Nichola J, Madison Joseph D, Fofanov Viacheslav Y, Pearson Talima, Sahl Jason W, Busch Joseph D, Weiner Zachary, Nally Jarlath E, Wagner David M, Rosenbaum Marieke H
The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, Arizona, United States of America.
National Veterinary Services Laboratories, APHIS, United States Department of Agriculture, Ames, Iowa, United States of America.
PLoS Negl Trop Dis. 2025 Apr 15;19(4):e0012966. doi: 10.1371/journal.pntd.0012966. eCollection 2025 Apr.
Leptospirosis (caused by pathogenic bacteria in the genus Leptospira) is prevalent worldwide but more common in tropical and subtropical regions. Transmission can occur following direct exposure to infected urine from reservoir hosts, or a urine-contaminated environment, which then can serve as an infection source for additional rats and other mammals, including humans. The brown rat, Rattus norvegicus, is an important reservoir of Leptospira spp. in urban settings. We investigated the presence of Leptospira spp. among brown rats in Boston, Massachusetts and hypothesized that rat population dynamics in this urban setting influence the transportation, persistence, and diversity of Leptospira spp. We analyzed DNA from 328 rat kidney samples collected from 17 sites in Boston over a seven-year period (2016-2022); 59 rats representing 12 of 17 sites were positive for Leptospira spp. We used 21 neutral microsatellite loci to genotype 311 rats and utilized the resulting data to investigate genetic connectivity among sampling sites. We generated whole genome sequences for 28 Leptospira spp. isolates obtained from frozen and fresh tissue from some of the 59 positive rat kidneys. When isolates were not obtained, we attempted genomic DNA capture and enrichment, which yielded 14 additional Leptospira spp. genomes from rats. We also generated an enriched Leptospira spp. genome from a 2018 human case in Boston. We found evidence of high genetic structure among rat populations that is likely influenced by major roads and/or other dispersal barriers, resulting in distinct rat population groups within the city; at certain sites these groups persisted for multiple years. We identified multiple distinct phylogenetic clades of L. interrogans among rats that were tightly linked to distinct rat populations. This pattern suggests L. interrogans persists in local rat populations and its transportation is influenced by rat population dynamics. Finally, our genomic analyses of the Leptospira spp. detected in the 2018 human leptospirosis case in Boston suggests a link to rats as the source. These findings will be useful for guiding rat control and human leptospirosis mitigation efforts in this and other similar urban settings.
钩端螺旋体病（由钩端螺旋体属的致病细菌引起）在全球范围内普遍存在，但在热带和亚热带地区更为常见。接触来自储存宿主的感染尿液或受尿液污染的环境后可能发生传播，而这些环境随后可能成为其他大鼠和包括人类在内的其他哺乳动物的感染源。褐家鼠（Rattus norvegicus）是城市环境中钩端螺旋体属的重要储存宿主。我们调查了马萨诸塞州波士顿褐家鼠中钩端螺旋体属的存在情况，并假设这种城市环境中的鼠类种群动态会影响钩端螺旋体属的传播、持久性和多样性。我们分析了在七年时间（2016 - 2022年）里从波士顿17个地点采集的328份鼠肾样本中的DNA；代表17个地点中12个地点的59只大鼠钩端螺旋体属呈阳性。我们使用21个中性微卫星位点对311只大鼠进行基因分型，并利用所得数据研究采样地点之间的遗传连通性。我们为从59只阳性鼠肾中的一些鼠的冷冻和新鲜组织中获得的28株钩端螺旋体属分离株生成了全基因组序列。当未获得分离株时，我们尝试进行基因组DNA捕获和富集，从大鼠中又获得了14个钩端螺旋体属基因组。我们还从2018年波士顿的一例人类病例中生成了一个富集的钩端螺旋体属基因组。我们发现鼠类种群之间存在高度遗传结构的证据，这可能受到主要道路和/或其他扩散障碍的影响，导致城市内形成不同的鼠类种群群体；在某些地点，这些群体持续存在多年。我们在大鼠中鉴定出多个不同的问号钩端螺旋体系统发育分支，它们与不同的鼠类种群紧密相连。这种模式表明问号钩端螺旋体在当地鼠类种群中持续存在，其传播受鼠类种群动态影响。最后，我们对2018年波士顿人类钩端螺旋体病病例中检测到的钩端螺旋体属进行的基因组分析表明与作为源头的大鼠存在关联。这些发现将有助于指导该城市及其他类似城市环境中的鼠类控制和人类钩端螺旋体病缓解工作。
