Salmonella Disrupts Host Endocytic Trafficking by SopD2-Mediated Inhibition of Rab7

• The effector SopD2 blocks delivery of endocytic cargo to lysosomes
• SopD2 interacts directly with host GTPase Rab7
• SopD2’s N terminus mediates both trafficking suppression and interaction with Rab7
• SopD2 impairs Rab7’s ability to bind cognate effectors RILP and FYCO1

SummaryIntracellular bacterial pathogens of a diverse nature share the ability to evade host immunity by impairing trafficking of endocytic cargo to lysosomes for degradation, a process that is poorly understood. Here, we show that the Salmonella enterica type 3 secreted effector SopD2 mediates this process by binding the host regulatory GTPase Rab7 and inhibiting its nucleotide exchange. Consequently, this limits Rab7 interaction with its dynein- and kinesin-binding effectors RILP and FYCO1 and thereby disrupts host-driven regulation of microtubule motors. Our study identifies a bacterial effector capable of directly binding and thereby modulating Rab7 activity and a mechanism of endocytic trafficking disruption that may provide insight into the pathogenesis of other bacteria. Additionally, we provide a powerful tool for the study of Rab7 function, and a potential therapeutic target.

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