Macropinosomes are Key Players in Early Shigella Invasion and Vacuolar Escape in Epithelial Cells

作者：Allon Weiner, Nora Mellouk, Noelia López-Montero, Yuen‐Yan Chang, Célia Souque, Christine Schmitt, Jost Enninga · 发表于：PLoS Pathogens · 年份：2016 · DOI：10.1371/journal.ppat.1005602 · 被引用次数：120 · 研究领域：Escherichia coli research studies、Bacterial Infections and Vaccines、Bacteriophages and microbial interactions

Intracellular pathogens include all viruses, many bacteria and parasites capable of invading and surviving within host cells. Key to survival is the subversion of host cell pathways by the pathogen for the purpose of propagation and evading the immune system. The intracellular bacterium Shigella flexneri, the causative agent of bacillary dysentery, invades host cells in a vacuole that is subsequently ruptured to allow growth of the pathogen within the host cytoplasm. S. flexneri invasion has been classically described as a macropinocytosis-like process, however the underlying details and the role of macropinosomes in the intracellular bacterial lifestyle have remained elusive. We applied dynamic imaging and advanced large volume correlative light electron microscopy (CLEM) to study the highly transient events of S. flexneri's early invasion into host epithelial cells and elucidate some of its fundamental features. First, we demonstrate a clear distinction between two compartments formed during the first step of invasion: the bacterial containing vacuole and surrounding macropinosomes, often considered identical. Next, we report a functional link between macropinosomes and the process of vacuolar rupture, demonstrating that rupture timing is dependent on the availability of macropinosomes as well as the activity of the small GTPase Rab11 recruited directly to macropinosomes. We go on to reveal that the bacterial containing vacuole and macropinosomes come into direct contact at...