Department of Biochemistry, Howard Hughes Medical Institute, Stanford University, Stanford, United States.
Department of Physics, University of California San Diego, San Diego, United States.
Elife. 2019 Feb 5;8:e40032. doi: 10.7554/eLife.40032.
hijacks host actin to promote its intracellular motility and intercellular spread. While virulence hinges on cell-to-cell spread, little is known about the dynamics of bacterial spread in epithelia at a population level. Here, we use live microscopy and statistical modeling to demonstrate that cell-to-cell spread proceeds anisotropically in an epithelial monolayer in culture. We show that boundaries of infection foci are irregular and dominated by rare pioneer bacteria that spread farther than the rest. We extend our quantitative model for bacterial spread to show that heterogeneous spreading behavior can improve the chances of creating a persistent infection in an actively extruding epithelium. Thus, our results indicate that cell-to-cell spread is heterogeneous, and that rare pioneer bacteria determine the frontier of infection foci and may promote bacterial infection persistence in dynamic epithelia.
This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
它劫持宿主肌动蛋白以促进其细胞内运动和细胞间传播。虽然毒力取决于细胞间传播,但关于细菌在群体水平上皮内的传播动力学知之甚少。在这里,我们使用活细胞显微镜和统计建模来证明,在培养的上皮单层中,细胞间传播是各向异性的。我们表明,感染灶的边界是不规则的,主要由传播距离超过其他细菌的罕见先驱细菌主导。我们将我们的细菌传播定量模型扩展到表明,异质传播行为可以提高在积极挤压上皮中产生持续感染的机会。因此,我们的结果表明,细胞间传播是异质的,罕见的先驱细菌决定了感染灶的前沿,并且可能在动态上皮中促进细菌感染的持续存在。
本文经过编辑过程,作者在该过程中决定如何处理同行评审中提出的问题。审稿人的评估是所有问题都已得到解决(见审稿意见)。