Department of Pathology, Stanford School of Medicine, Stanford University, Stanford, CA, USA.
Molecular Immunology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
Methods Mol Biol. 2022;2387:105-108. doi: 10.1007/978-1-0716-1779-3_11.
The acquisition by a Mycobacterium marinum-like progenitor of a plasmid encoding enzymes for the biosynthesis of the highly potent macrolide toxin mycolactone has set off the evolution of M. ulcerans toward a new mycobacterial species. While the selective advantage of producing mycolactone for survival in environmental niche(s) of the pathogen is unclear, there is no doubt that the cytotoxic, immunomodulatory, and analgesic properties of mycolactone are key for the establishment and progression of M. ulcerans infections in the host. Improved procedures for the isolation, handling, and detection of the amphiphilic and light-sensitive toxin have facilitated studies to unravel molecular mechanisms of mycolactone action on host cells in vitro and on cellular and immune responses in animal models. The pivotal role of mycolactone in the pathology of Buruli ulcer and the fact that the toxin has not been associated with other pathogens make it an ideal target for therapeutics/vaccines aiming at mycolactone neutralization and for the development of assays for the diagnosis of the disease.
一种类似于海分枝杆菌的前体菌获得了编码用于合成强效大环内酯毒素(mycolactone)的生物合成酶的质粒，这引发了溃疡分枝杆菌向新的分枝杆菌物种的进化。虽然在病原体的环境小生境中产生 mycolactone 以生存的选择优势尚不清楚，但毫无疑问，mycolactone 的细胞毒性、免疫调节和镇痛特性是分枝杆菌溃疡感染在宿主中建立和进展的关键。改进的分离、处理和检测亲脂性和光敏感毒素的程序，促进了研究，以揭示 mycolactone 对体外宿主细胞以及动物模型中细胞和免疫反应的作用的分子机制。mycolactone 在布吕利溃疡病理中的关键作用，以及该毒素与其他病原体无关这一事实，使其成为针对 mycolactone 中和的治疗方法/疫苗的理想靶点，并为该疾病的诊断开发检测方法。
