Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain; Pulmobiotics Ltd, Dr. Aiguader 88, Barcelona 08003, Spain; Institute of Biotechnology and Biomedicine "Vicent Villar Palasi" (IBB), Universitat Autònoma de Barcelona, Barcelona, Spain.
Microbes Infect. 2024 Jul-Aug;26(5-6):105342. doi: 10.1016/j.micinf.2024.105342. Epub 2024 Apr 26.
A non-pathogenic Mycoplasma pneumoniae-based chassis is leading the development of live biotherapeutic products (LBPs) for respiratory diseases. However, reports connecting Guillain-Barré syndrome (GBS) cases to prior M. pneumoniae infections represent a concern for exploiting such a chassis. Galactolipids, especially galactocerebroside (GalCer), are considered the most likely M. pneumoniae antigens triggering autoimmune responses associated with GBS development. In this work, we generated different strains lacking genes involved in galactolipids biosynthesis. Glycolipid profiling of the strains demonstrated that some mutants show a complete lack of galactolipids. Cross-reactivity assays with sera from GBS patients with prior M. pneumoniae infection showed that certain engineered strains exhibit reduced antibody recognition. However, correlation analyses of these results with the glycolipid profile of the engineered strains suggest that other factors different from GalCer contribute to sera recognition, including total ceramide levels, dihexosylceramide (DHCer), and diglycosyldiacylglycerol (DGDAG). Finally, we discuss the best candidate strains as potential GBS-free Mycoplasma chassis.
基于无致病性肺炎支原体的底盘正在引领治疗呼吸系统疾病的活体生物治疗产品（LBPs）的开发。然而，将格林-巴利综合征（GBS）病例与先前的肺炎支原体感染联系起来的报告，引起了人们对利用这种底盘的关注。半乳糖脂，特别是半乳糖脑苷脂（GalCer），被认为是最有可能引发与 GBS 发展相关的自身免疫反应的肺炎支原体抗原。在这项工作中，我们生成了缺乏参与半乳糖脂生物合成的基因的不同菌株。对菌株的糖脂分析表明，一些突变体完全缺乏半乳糖脂。与先前感染过肺炎支原体的 GBS 患者的血清进行交叉反应性测定表明，某些工程菌株的抗体识别能力降低。然而，这些结果与工程菌株的糖脂图谱的相关性分析表明，除了 GalCer 之外，其他因素也会导致血清识别，包括总神经酰胺水平、二己糖神经酰胺（DHCer）和双糖基二酰基甘油（DGDAG）。最后，我们讨论了作为潜在无 GBS 肺炎支原体底盘的最佳候选菌株。
