Genomic Correlates with Differential Virulence in Melioidosis Animal Models

假鼻疽伯克霍尔德氏菌通常在泰国和澳大利亚(但也在其他赤道地区)观察到 死亡率分别为40%和14%。这些死亡率的差异是 归因于医疗质量(28)，但我们的数据表明，病原体种群在 这些地区(145个)。此外，澳大利亚的前瞻性临床研究正在进行，前景看好。 菌株类型和结果之间的初步关联(Currie，Tuanyok，Wagner，Keim等人， 未发布的数据)。众所周知，假鼻疽杆菌含有一个“开放”的基因组(90)，它可以重组 在很高的频率下，导致病原体种群内部和之间的巨大多样性。我们相信差异化 病原体群体(菌株)的毒力导致了全球不同的死亡率。 我们的主要假设是高度多样化的假鼻疽杆菌菌株具有不同的毒力水平，并且 这些毒力差异将取决于菌株的基因组组成(例如基因组岛)。 已经记录了多种感染途径。类鼻疽的感染途径往往很难 在临床上确定，但吸入和经皮途径都会发生。类鼻疽发病率上升 在热带风暴和濒临溺水之后(30，31)，与肺部路线一致。然而，大多数 类鼻疽病例可能是由经皮接种(39)引起的，这与存在 皮肤脓肿和皮肤损害(28例)。毒力因动物感染途径不同而不同 取决于特定的菌株(见CK#3和(11,146))。 动物模型很重要。由于人体研究可能会有问题，动物模型是一种 了解病原菌毒力的常用而有力的研究方法。鼠标是最便宜的 模型是一个非常强大的模型，但单个模型并不总是准确地代表其他疾病 动物，包括人类。开发其他动物模型(例如，多个小鼠品系、大鼠、非人类 灵长类动物)可以支持对小鼠的初步研究，并使我们对疾病有更多的了解 对人类疾病干预具有普遍性和代表性。对动物的认识和理解 模型对传染病研究至关重要。

Burkholderia pseudomallei, are commonly observed in Thailand and Australia (but also other equatorial regions), where mortality rates are 40% and 14%, respectively. The difference in these mortality rates has been attributed to healthcare quality (28), but our data demonstrate that pathogen populations also differ between these regions (145). In addition, prospective clinical studies in Australia are under way with promising preliminary associations between strain types and outcomes (Currie, Tuanyok, Wagner, Keim, et al., unpublished data). It is well established that B. pseudomallei contains an "open" genome (90) that recombines at a high frequency, leading to great diversity within and among pathogen populations. We believe differential virulence among pathogen populations (strains) contributes to differential mortality rates around the globe. Our primary hypothesis is that highly diverse B. pseudomallei strains have different virulence levels, and that these virulence differences will depend on the strain genomic composition (e.g., genomic islands). Multiple infection routes have been documented. Melioidosis infection routes are frequently hard to determine in the clinic, but inhalational and percutaneous routes both occur. Melioidosis incidence increases following tropical storms and near-drowning (30, 31), consistent with a pulmonary route. However, most melioidosis cases probably result from percutaneous inoculation (39), which is consistent with the presence of skin abscesses and dermal lesions (28). Virulence varies according to the infective route in animals and depends on the particular strain (see CK#3 and (11,146)). Animal models are important. Because human studies can be problematic, animal models are a common and powerful research approach to understand pathogen virulence. The mouse is the least expensive model, yet a very powerful one, but a single model may not always accurately represent diseases in other animals, including humans. Developing additional animal models (e.g., multiple mouse strains, rat, nonhuman primates) can support initial studies in the mouse and make our disease understanding more generalized and representative for human disease intervention. Knowledge and understanding of animal models is critical to infectious disease research.