Search

The facultative intracellular pathogen Shigella flexneri invades non-phagocytic epithelial gut cells. Through a syringe-like apparatus called type 3 secretion system, it injects effector proteins into the host cell triggering actin rearrangements leading to its uptake within a tight vacuole, termed the bacterial-containing vacuole (BCV). Simultaneously, Shigella induces the formation of large vesicles around the entry site, which we refer to as infection-associated macropinosomes (IAMs). After entry, Shigella ruptures the BCV and escapes into the host cytosol by disassembling the BCV remnants. Previously, IAM formation has been shown to be required for efficient BCV escape, but the molecular events associated with BCV disassembly have remained unclear. To identify host components required for BCV disassembly, we performed a microscopy-based screen to monitor the recruitment of BAR domain-containing proteins, which are a family of host proteins involved in membrane shaping and sensing (e.g. endocytosis and recycling) during Shigella epithelial cell invasion. We identified endosomal recycling BAR protein Sorting Nexin-8 (SNX8) localized to IAMs in a PI(3)P-dependent manner before BCV disassembly. At least two distinct IAM subpopulations around the BCV were found, either being recycled back to cellular compartments such as the plasma membrane or transitioning to become RAB11A positive "contact-IAMs" involved in promoting BCV rupture. The IAM subpopulation duality was marked by the exclusive recruitment of either SNX8 or RAB11A. Hindering PI(3)P production at the IAMs led to an inhibition of SNX8 recruitment at these compartments and delayed both, the step of BCV rupture time and successful BCV disassembly. Finally, siRNA depletion of SNX8 accelerated BCV rupture and unpeeling of BCV remnants, indicating that SNX8 is involved in controlling the timing of the cytosolic release. Overall, our work sheds light on how Shigella establishes its intracellular niche through the subversion of a specific set of IAMs., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Numerous bacterial pathogens "confine" themselves within host cells with an intracellular localization as main or exclusive niche. Many of them switch dynamically between a membrane-bound or cytosolic lifestyle. This requires either membrane damage and/or repair of the bacterial-containing compartment. Niche switching has profound consequences on how the host cell recognizes the pathogens in time and space for elimination. Moreover, niche switching impacts how bacteria communicate with host cells to obtain nutrients, and it affects the accessibility to antibiotics. Understanding the local environments and cellular phenotypes that lead to niche switching is critical for developing new host-targeted antimicrobial strategies, and has the potential to shed light into fundamental cellular processes., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Only a profound understanding of the structure and function of cells - either as single units or in the context of tissues and whole organisms - will allow a comprehension of what happens in pathological conditions and provides the means to fight disease. The Cell Biology and Infection (BCI for Biologie Cellulaire et Infection) department was created in 2002 at the Institut Pasteur in Paris to develop a research program under the umbrella of cell biology, infection biology and microbiology. Its visionary ambition was to shape a common framework for cellular microbiology, and to interface the latter with hard sciences like physics and mathematics and cutting-edge technology. This concept, ahead of time, has given high visibility to the field of cellular microbiology and quantitative cell biology, and it has allowed the successful execution of highly interdisciplinary research programs linking a molecular understanding of cellular events with disease. Now, the BCI department embraces additional pathologies, namely cancer and neurodegenerative diseases. Here, we will portray how the integrative research approach of BCI has led to major scientific breakthroughs during the last ten years, and where we see scientific opportunities for the near future., (Copyright © 2019 Springer Nature Limited. Published by Elsevier Masson SAS.. All rights reserved.)