title: A Rab32-dependent pathway contributes to Salmonella typhi host restriction.
abstract: Unlike other Salmonellae, the intracellular bacterial human pathogen Salmonella Typhi exhibits strict host specificity. The molecular bases for this restriction are unknown. Here we found that the expression of a single type III secretion system effector protein from broad-host Salmonella Typhimurium allowed Salmonella Typhi to survive and replicate within macrophages and tissues from mice, a nonpermissive host. This effector proteolytically targeted Rab32, which controls traffic to lysosome-related organelles in conjunction with components of the biogenesis of lysosome-related organelle complexes (BLOCs). RNA interference-mediated depletion of Rab32 or of an essential component of a BLOC complex was sufficient to allow S. Typhi to survive within mouse macrophages. Furthermore, S. Typhi was able to survive in macrophages from mice defective in BLOC components.
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
authors.forename: Stefania
authors.initials: S
authors.lastname: Spanò
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Galán
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D058947:Bacterial Secretion Systems / Q000235:genetics / Q000502:physiology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D054884:Host-Pathogen Interactions; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010802:Phylogeny; D034622:RNA Interference; D012485:Salmonella typhi / Q000235:genetics / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000145:classification / Q000235:genetics / Q000502:physiology*
chemical_list: D058947:Bacterial Secretion Systems; C478766:Rab32 protein, mouse; D020691:rab GTP-Binding Proteins