title: Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host Salmonella.
abstract: Unlike broad-host Salmonella serovars, which cause self-limiting disease, Salmonella enterica serovar Typhi can infect only humans causing typhoid fever, a life-threatening systemic disease. The molecular bases for these differences are presently unknown. Here we show that the GTPase Rab29 (Rab7L1) distinguishes the intracellular vacuole of human-adapted and broad-host Salmonella serovars. A screen to identify host factors required for the export of typhoid toxin, which is exclusively encoded by the human-specific Salmonella enterica serovars Typhi (S. Typhi) and Paratyphi (S. Paratyphi) identified Rab29. We found that Rab29 is recruited to the S. Typhi-containing vacuole but not to vacuoles containing broad-host Salmonella. We observed that in cells infected with broad-host Salmonella Rab29 is specifically cleaved by the proteolytic activity of GtgE, a unique type III secretion effector protein that is absent from S. Typhi. An S. Typhi strain engineered to express GtgE and therefore able to cleave Rab29 exhibited increased intracellular replication in human macrophages. These findings indicate significant differences in the intracellular biology of human-adapted and broad-host Salmonella and show how subtle differences in the assortment of effector proteins encoded by highly related pathogens can have a major impact in their biology.
authors: Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
authors: Stefania
authors: S
authors: Spanò
authors: Xiaoyun
authors: X
authors: Liu
authors: Jorge E
authors: JE
authors: Galán
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002451:Cell Compartmentation; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D059748:Proteolysis; D012475:Salmonella / Q000254:growth & development / Q000502:physiology*; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: D020691:rab GTP-Binding Proteins