Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, USA.
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Curr Opin Microbiol. 2023 Apr;72:102266. doi: 10.1016/j.mib.2023.102266. Epub 2023 Feb 4.
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), accounts for over ten million infections and over 1.5 million deaths every year [1]. Upon infection, the seesaw between Mtb and our immune systems creates microenvironments that are compositionally distinctive and changing over time. While the field has begun to better understand the spatial complexity of TB disease, our understanding and experimental dissection of the temporal dynamics of TB and TB drug treatment is much more rudimentary. However, it is the combined spatiotemporal heterogeneity of TB disease that creates niches and time windows within which the pathogen can survive and thrive during treatment. Here, we review the emerging data on the interactions of spatial and temporal dynamics as they relate to TB disease and treatment. A better understanding of the interactions of Mtb, host, and antibiotics through space and time will elucidate treatment failure and potentially identify opportunities for new TB treatment regimens.
结核分枝杆菌(Mtb)是结核病(TB)的病原体,每年导致超过 1000 万人感染和超过 150 万人死亡[1]。在感染后,Mtb 和我们的免疫系统之间的拉锯战创造了成分独特且随时间变化的微环境。虽然该领域已经开始更好地理解结核病疾病的空间复杂性,但我们对结核病和结核病药物治疗的时间动态的理解和实验剖析要原始得多。然而,正是结核病疾病的时空异质性的综合,为病原体在治疗期间生存和繁殖创造了小生境和时间窗口。在这里,我们回顾了与结核病疾病和治疗相关的空间和时间动态相互作用的新兴数据。通过空间和时间更好地理解 Mtb、宿主和抗生素的相互作用,将阐明治疗失败的原因,并有可能为新的结核病治疗方案确定机会。