Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
Victorian Infectious Diseases Service, Royal Melbourne Hospital, Parkville, Victoria, Australia.
PLoS Negl Trop Dis. 2024 May 3;18(5):e0011979. doi: 10.1371/journal.pntd.0011979. eCollection 2024 May.
Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A controlled human infection model has the potential to accelerate our knowledge of the immunological correlates of disease, to test prophylactic interventions and novel therapeutics. Here we present microbiological evidence supporting M. ulcerans JKD8049 as a suitable human challenge strain. This non-genetically modified Australian isolate is susceptible to clinically relevant antibiotics, can be cultured in animal-free and surfactant-free media, can be enumerated for precise dosing, and has stable viability following cryopreservation. Infectious challenge of humans with JKD8049 is anticipated to imitate natural infection, as M. ulcerans JKD8049 is genetically stable following in vitro passage and produces the key virulence factor, mycolactone. Also reported are considerations for the manufacture, storage, and administration of M. ulcerans JKD8049 for controlled human infection.
关于引起被忽视热带病—— 溃疡分枝杆菌病（BU）的病原体溃疡分枝杆菌的感染，仍存在一些关键的科学问题。人体感染控制模型有可能加速我们对疾病免疫相关性的认识，从而对预防性干预措施和新疗法进行测试。在这里，我们提出了微生物学证据，支持溃疡分枝杆菌 JKD8049 作为合适的人体挑战株。这种非基因修饰的澳大利亚分离株对临床相关抗生素敏感，可在无动物和无表面活性剂的培养基中培养，可通过计数进行精确给药，并且在冷冻保存后具有稳定的活力。预计用 JKD8049 对人类进行感染性挑战将模拟自然感染，因为溃疡分枝杆菌 JKD8049 在体外传代后遗传稳定，并产生关键的毒力因子—— 分枝菌酸内酯。本文还报告了用于人体感染控制的 JKD8049 的制造、储存和管理的注意事项。
