Salmonella effector SopD2 interferes with Rab34 function

Abstract

Many intracellular pathogens have evolved highly specialized mechanisms to isolate themselves from the host cell's innate immune response while still obtaining the necessary nutrients to survive. Salmonella utilizes type 3 secretion systems (T3SSs) to deliver bacterial proteins called effectors, across the encompassing Salmonella Containing vacuole (SCV) membrane, to subvert the host's membrane trafficking pathways and alter other cellular processes. The Salmonella Pathogenicity Island (SPI)-2 effector SopD2 has recently been demonstrated to modulate multiple members of the Rab GTPase family such as Rab7, Rab8, Rab10, and Rab32 (D'Costa et al., , Cell Reports, 12:1508-18; Spano et al., , Cell Host & Microbe, 19:216-26). Here, we demonstrate the additional capacity of SopD2 to bind Rab34 and modulate its function. Our data indicate that depletion of Rab34 delays maturation of the SCV, and consequently, inhibits intracellular Salmonella enterica serotype typhimurium (S. typhimurium) growth. Interestingly, intracellular growth of the S. typhimurium lacking SopD2 was severely impaired in Rab34-depleted cells, suggesting a compounding virulence effect. Overall this study reveals an additional member of the Rab GTPase family, Rab34, that is modulated by SopD2 and provides insight into its role in Salmonella biology.

Salmonella effector SopD promotes plasma membrane scission by inhibiting Rab10

“…Typhimurium invasion. Our findings are consistent with prior studies indicating that the related effector SopD2 can inhibit the activity of multiple Rab GTPases 20 – 22 . We also show that the catalytic arginine residue required for the GAP activity of SopD2 21 is present in its paralog SopD and necessary for its GAP activity towards Rab10.…”

“…SopD shares 42% sequence identity with another effector, SopD2 19 , which is secreted by the SPI-2 T3SS and is involved in later stages of infection. SopD2 binds to and inactivates several Rab GTPases through multiple mechanisms [20][21][22] . Whether SopD can also modulate Rab GTPase function is unknown.…”

Regulation of the small GTPase Rab1 function by a bacterial glucosyltransferase

“…1a ). SopD2, a type III effector of Salmonella Typhimurium, was included as a positive control for our approach as it has been shown to interact with multiple small Rab GTPases 24 – 26 . The efficiency of cross-linking reactions was monitored by immunoblotting analyses.…”

Rab20 is critical for bacterial lipoprotein tolerization-enhanced bactericidal activity in macrophages during bacterial infection

“…It has been revealed that the Rab5-Rab34 and Rab31-Rab7 cascades likely represent two distinct endosomal or phagosomal maturation pathways in dendritic cells (Li et al, 2016). Consistent with the independence of Rab34 from Rab7, Rab7 is capable of associating with the Salmonella-containing vacuole in HeLa cells with Rab34 depletion (Teo et al, 2017). Therefore, it will be intriguing to investigate whether the Rab31-Rab7 pathway is more important than the Rab5-Rab34 pathway in regulating phagosome maturation in BLP-tolerized macrophages; which may serve as the key players in maintaining the balance of antimicrobial capacity in BLP-tolerized macrophages.…”