Mammalian Cell Entry domains are required for bile resistance and virulence inSalmonella

AbstractMCE domains were first reported inMycobacteriaas having a role inMammalianCellEntry, with subsequent studies showing their importance during infection. Here, we have examined the function of MCE proteins inSalmonellaTyphimurium during mammalian infection. We report that MCE proteins are required forSalmonellavirulence, but that this is not related to decreased adherence, entry or survival in mammalian cells. Instead, we reveal that MCE proteins are required forSalmonellabile resistance, in particular to withstand bile salts such as cholate and deoxycholate. Based on our previous work inEscherichia coli, and other studies that have reported roles for MCE proteins in membrane biogenesis, we propose thatSalmonellalacking MCE domains have a defective outer membrane that results in bile sensitivity and decreased virulencein vivo. These results suggest that MCE domains mediate fundamental aspects of bacterial membrane physiology as opposed to a proposed direct role in mammalian cell entry, explaining their conservation across both pathogenic and non-pathogenic bacteria.