Genomic Correlates with Differential Virulence in Melioidosis Animal Models

类鼻疽动物模型中基因组与差异毒力的相关性

• 批准号: 8260261
• 负责人: Paul Stephen Keim
• 金额: $ 34.6万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8260261
• 关键词: Animal Model; Animals; Australia; Burkholderia pseudomallei; Clinic; Clinical Research; Collection; Data; Dermal; Differential Mortality; Disease; Emerging Communicable Diseases; Frequencies; Gene Expression; Genome; Genomic Islands; Genomics; Genotype; Human; Inbred Mouse; Incidence; Infection; Infectious Diseases Research; Intervention; Knowledge; Lesion; Lung; Melioidosis; Modeling; Mouse Strains; Mus; Near Drowning; Outcome; Pattern; Phenotype; Population; Proteomics; Rattus; Research; Resolution; Route; Surveys; Thailand; Virulence; Virulence Factors; biodefense; health care quality; human disease; knockout gene; mortality; nonhuman primate; pathogen; prospective; skin abscess

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way with promising preliminary associations between strain types and outcomes (Currie, Tuanyok, Wagner, Keim, et al., unpublished data).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.

假马里伯克霍尔德氏菌，常见于泰国和澳大利亚（但也见于其他赤道地区）