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一种非结核分枝杆菌可能解开瑞士巴塞尔方济各教堂女士的神秘死因之谜。

A nontuberculous mycobacterium could solve the mystery of the lady from the Franciscan church in Basel, Switzerland.

机构信息

Eurac Research - Institute for Mummy Studies, 39100, Bolzano, Italy.

Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, 4031, Basel, Switzerland.

出版信息

BMC Biol. 2023 Feb 7;21(1):9. doi: 10.1186/s12915-022-01509-7.

Abstract

BACKGROUND

In 1975, the mummified body of a female has been found in the Franciscan church in Basel, Switzerland. Molecular and genealogic analyses unveiled her identity as Anna Catharina Bischoff (ACB), a member of the upper class of post-reformed Basel, who died at the age of 68 years, in 1787. The reason behind her death is still a mystery, especially that toxicological analyses revealed high levels of mercury, a common treatment against infections at that time, in different body organs. The computed tomography (CT) and histological analysis showed bone lesions in the femurs, the rib cage, and the skull, which refers to a potential syphilis case.

RESULTS

Although we could not detect any molecular signs of the syphilis-causing pathogen Treponema pallidum subsp. pallidum, we realized high prevalence of a nontuberculous mycobacterium (NTM) species in brain tissue sample. The genome analysis of this NTM displayed richness of virulence genes and toxins, and similarity to other infectious NTM, known to infect immunocompromised patients. In addition, it displayed potential resistance to mercury compounds, which might indicate a selective advantage against the applied treatment. This suggests that ACB might have suffered from an atypical mycobacteriosis during her life, which could explain the mummy's bone lesion and high mercury concentrations.

CONCLUSIONS

The study of this mummy exemplifies the importance of employing differential diagnostic approaches in paleopathological analysis, by combining classical anthropological, radiological, histological, and toxicological observations with molecular analysis. It represents a proof-of-concept for the discovery of not-yet-described ancient pathogens in well-preserved specimens, using de novo metagenomic assembly.

摘要

背景

1975 年,一具女性木乃伊在瑞士巴塞尔的方济各会教堂被发现。分子和基因分析揭示了她的身份是安娜·卡塔琳娜·比肖夫(ACB),她是后改革时期巴塞尔上层社会的一员,于 1787 年去世,享年 68 岁。她的死因仍然是个谜,特别是毒理学分析显示,在不同的身体器官中都有高浓度的汞,这是当时常见的抗感染治疗方法。计算机断层扫描(CT)和组织学分析显示股骨、肋骨和颅骨有骨损伤,这表明可能患有梅毒。

结果

尽管我们未能检测到引起梅毒的病原体苍白密螺旋体亚种的任何分子迹象,但我们在脑组织样本中发现了一种非结核分枝杆菌(NTM)的高流行率。这种 NTM 的基因组分析显示出丰富的毒力基因和毒素,与其他已知感染免疫功能低下患者的传染性 NTM 相似。此外,它显示出对汞化合物的潜在耐药性,这可能表明它对应用的治疗方法具有选择性优势。这表明 ACB 可能在其一生中患有非典型分枝杆菌病,这可以解释木乃伊的骨损伤和高汞浓度。

结论

对这具木乃伊的研究说明了在进行古病理学分析时采用差异化诊断方法的重要性,将经典的人类学、放射学、组织学和毒理学观察与分子分析相结合。它代表了使用从头组装的宏基因组学在保存完好的标本中发现尚未描述的古代病原体的概念验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3df7/9903526/84d8512db16e/12915_2022_1509_Fig1_HTML.jpg

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