School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), 1015 Lausanne, Switzerland.
School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), 1015 Lausanne, Switzerland.
Cell Rep. 2021 Jul 20;36(3):109351. doi: 10.1016/j.celrep.2021.109351.
Recurrence of uropathogenic Escherichia coli (UPEC) infections has been attributed to reactivation of quiescent intracellular reservoirs (QIRs) in deep layers of the bladder wall. QIRs are thought to arise late during infection following dispersal of bacteria from intracellular bacterial communities (IBCs) in superficial umbrella cells. Here, we track the formation of QIR-like bacteria in a bladder organoid model that recapitulates the stratified uroepithelium within a volume suitable for high-resolution live-cell imaging. Bacteria injected into the organoid lumen enter umbrella-like cells and proliferate to form IBC-like bodies. In parallel, single bacteria penetrate deeper layers of the organoid wall, where they localize within or between uroepithelial cells. These "solitary" bacteria evade killing by antibiotics and neutrophils and are morphologically distinct from bacteria in IBCs. We conclude that bacteria with QIR-like properties may arise at early stages of infection, independent of IBC formation and rupture.
尿路致病性大肠杆菌 (UPEC) 感染的复发归因于膀胱壁深层静止细胞内储库 (QIR) 的重新激活。QIR 被认为是在细菌从浅层伞状细胞内细菌群落 (IBC) 中扩散后，在感染后期出现的。在这里，我们在膀胱类器官模型中追踪 QIR 样细菌的形成，该模型在适合高分辨率活细胞成像的体积内重现了分层尿路上皮。注入类器官腔的细菌进入伞状细胞并增殖形成 IBC 样体。与此同时，单个细菌穿透类器官壁的深层，在那里它们定位于尿路上皮细胞内或细胞之间。这些“孤立”的细菌逃避抗生素和中性粒细胞的杀伤，并且在形态上与 IBC 中的细菌不同。我们得出结论，具有 QIR 样特性的细菌可能在感染的早期阶段出现，与 IBC 的形成和破裂无关。
