10 April 2024 | Hongxian Zhu, Andrew M. Sydor, Kirsten C. Boddy, Etienne Coyaud, Estelle M. N. Laurent, Aaron Au, Joel M. J. Tan, Bing-Ru Yan, Jason Moffat, Aleixo M. Muise, Christopher M. Yip, Sergio Grinstein, Brian Raught, John H. Brumell
Salmonella, a gram-negative intracellular pathogen, uses a type 3 secretion system (T3SS) to translocate virulence proteins (effectors) into host cells, modulating host cell machinery to facilitate bacterial uptake into vacuoles. A key feature of Salmonella invasion is the formation of actin-rich ruffles on the host cell surface, which contribute to bacterial uptake. However, the source of these ruffles and how Salmonella regulates membrane mobilization within host cells remains unclear. This study reveals that Salmonella exploits pre-existing tubular compartments associated with the plasma membrane (PM) as membrane reservoirs for the generation of invasion ruffles. These reservoirs are formed through the activity of RAB10 GTPase and contain the exocyst subunit EXOC2. During infection, the SPI-1 T3SS effectors SipC, SopE2, and SopB recruit exocyst subunits from these reservoirs and other cellular compartments, enabling exocyst complex assembly and membrane delivery required for bacterial uptake. The findings highlight the importance of RAB10 in establishing membrane reservoirs and how Salmonella can exploit these compartments during host cell invasion.Salmonella, a gram-negative intracellular pathogen, uses a type 3 secretion system (T3SS) to translocate virulence proteins (effectors) into host cells, modulating host cell machinery to facilitate bacterial uptake into vacuoles. A key feature of Salmonella invasion is the formation of actin-rich ruffles on the host cell surface, which contribute to bacterial uptake. However, the source of these ruffles and how Salmonella regulates membrane mobilization within host cells remains unclear. This study reveals that Salmonella exploits pre-existing tubular compartments associated with the plasma membrane (PM) as membrane reservoirs for the generation of invasion ruffles. These reservoirs are formed through the activity of RAB10 GTPase and contain the exocyst subunit EXOC2. During infection, the SPI-1 T3SS effectors SipC, SopE2, and SopB recruit exocyst subunits from these reservoirs and other cellular compartments, enabling exocyst complex assembly and membrane delivery required for bacterial uptake. The findings highlight the importance of RAB10 in establishing membrane reservoirs and how Salmonella can exploit these compartments during host cell invasion.