Proteomic Analysis of Salmonella-modified Membranes Reveals Adaptations to Macrophage Hosts

Abstract

Systemic infection and proliferation of intracellular pathogens require the biogenesis of a growth-stimulating compartment. The gastrointestinal pathogen <i>Salmonella enterica</i> commonly forms highly dynamic and extensive tubular membrane compartments built from <i>Salmonella</i>-modified membranes (SMMs) in diverse host cells. Although the general mechanism involved in the formation of replication-permissive compartments of <i>S. enterica</i> is well researched, much less is known regarding specific adaptations to different host cell types. Using an affinity-based proteome approach, we explored the composition of SMMs in murine macrophages. The systematic characterization provides a broader landscape of host players to the maturation of <i>Salmonella</i>-containing compartments and reveals core host elements targeted by <i>Salmonella</i> in macrophages as well as epithelial cells. However, we also identified subtle host specific adaptations. Some of these observations, such as the differential involvement of the COPII system, Rab GTPases 2A, 8B, 11 and ER transport proteins Sec61 and Sec22B may explain cell line-dependent variations in the pathophysiology of <i>Salmonella</i> infections. In summary, our system-wide approach demonstrates a hitherto underappreciated impact of the host cell type in the formation of intracellular compartments by <i>Salmonella</i>.