The SPI-2 type III secretion system restricts motility of Salmonella-containing vacuoles

Intracellular replication of Salmonella enterica occurs in membrane-bound compartments, called Salmonella-containing vacuoles (SCVs). Following invasion of epithelial cells, most SCVs migrate to a perinuclear region and replicate in close association with the Golgi network. The association of SCVs with the Golgi is dependent on the Salmonella-pathogenicity island-2 (SPI-2) type III secretion system (T3SS) effectors SseG, SseF and SifA. However, little is known about the dynamics of SCV movement. Here, we show that in epithelial cells, 2 h were required for migration of the majority of SCVs to within 5 μm from the microtubule organizing centre (MTOC), which is located in the same subcellular region as the Golgi network. This initial SCV migration was saltatory, bidirectional and microtubule-dependent. An intact Golgi, SseG and SPI-2 T3SS were dispensable for SCV migration to the MTOC, but were essential for maintenance of SCVs in that region. Live-cell imaging between 4 and 8 h post invasion revealed that the majority of wild-type SCVs displaced less than 2 μm in 20 min from their initial starting positions. In contrast, between 6 and 8 h post invasion the majority of vacuoles containing sseG, sseF or ssaV mutant bacteria displaced more than 2 μm in 20 min from their initial starting positions, with some undergoing large and dramatic movements. Further analysis of the movement of SCVs revealed that large displacements were a result of increased SCV speed rather than a change in their directionality, and that SseG influences SCV motility by restricting vacuole speed within the MTOC/Golgi region. SseG might function by tethering SCVs to Golgi-associated molecules, or by controlling microtubule motors, for example by inhibiting kinesin recruitment or promoting dynein recruitment

Challenges in assessing and managing multi-hazard risks: A European stakeholders perspective

The latest evidence suggests that multi-hazards and their interrelationships (e.g., triggering, compound, and consecutive hazards) are becoming more frequent across Europe, underlying a need for resilience building by moving from single-hazard-focused to multi-hazard risk assessment and management. Although significant advancements were made in our understanding of these events, mainstream practice is still focused on risks due to single hazards (e.g., flooding, earthquakes, droughts), with a limited understanding of the stakeholder needs on the ground. To overcome this limitation, this paper sets out to understand the challenges for moving towards multi-hazard risk management through the perspective of European stakeholders. Based on five workshops across different European pilots (Danube Region, Veneto Region, Scandinavia, North Sea, and Canary Islands) and an expert workshop, we identify five prime challenges: i) governance, ii) knowledge of multi-hazards and multi-risks, iii) existing approaches to disaster risk management, iv) translation of science to policy and practice, and v) lack of data. These challenges are inherently linked and cannot be tackled in isolation with path dependency posing a significant hurdle in transitioning from single- to multi-hazard risk management. Going forward, we identify promising approaches for overcoming some of the challenges, including emerging approaches for multi-hazard characterisation, a common understanding of terminology, and a comprehensive framework for guiding multi-hazard risk assessment and management. We argue for a need to think beyond natural hazards and include other threats in creating a comprehensive overview of multi-hazard risks, as well as promoting thinking of multi-hazard risk reduction in the context of larger development goals