Yu Jiayu, Liu Yang, Yin Huijia, Chang Zengyi
1The State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, 100871 Beijing, China.
2Center for Protein Science, Peking University, 100871 Beijing, China.
Cell Discov. 2019 Jan 22;5:8. doi: 10.1038/s41421-019-0080-3. eCollection 2019.
Bacteria have long been recognized to be capable of entering a phenotypically non-growing persister state, in which the cells exhibit an extended regrowth lag and a multidrug tolerance, thus posing a great challenge in treating infectious diseases. Owing to their non-inheritability, low abundance of existence, lack of metabolic activities, and high heterogeneity, properties of persisters remain poorly understood. Here, we report our accidental discovery of a subcellular structure that we term the regrowth-delay body, which is formed only in non-growing bacterial cells and sequesters multiple key proteins. This structure, that dissolves when the cell resumes growth, is able to be viewed as a marker of persisters. Our studies also indicate that persisters exhibit different depth of persistence, as determined by the status of their regrowth-delay bodies. Our findings imply that suppressing the formation and/or promoting the dissolution of regrowth-delay bodies could be viable strategies for eradicating persisters.
长期以来,人们一直认识到细菌能够进入一种表型上不生长的持留菌状态,在此状态下,细胞表现出延长的再生长延迟和多重耐药性,从而在治疗传染病方面构成巨大挑战。由于其不可遗传性、存在丰度低、缺乏代谢活性以及高度异质性,持留菌的特性仍知之甚少。在此,我们报告意外发现了一种亚细胞结构,我们将其命名为再生长延迟体,它仅在不生长的细菌细胞中形成,并隔离多种关键蛋白。这种结构在细胞恢复生长时溶解,可被视为持留菌的标志物。我们的研究还表明,持留菌表现出不同的持留深度,这由它们再生长延迟体的状态决定。我们的发现意味着抑制再生长延迟体的形成和/或促进其溶解可能是根除持留菌的可行策略。