Salmonella inhibits retrograde trafficking of mannose-6-phosphate receptors and lysosome function

Kieran McGourty, Teresa L. Thurston, Sophie A. Matthews, Laurie Pinaud, Luís Jaime Mota, David W. Holden

Research output: Contribution to journalArticlepeer-review

104 Citations (Scopus)

Abstract

Salmonella enterica is an intracellular bacterial pathogen that replicates within membrane-bound vacuoles through the action of effector proteins translocated into host cells. Salmonella vacuoles have characteristics of lysosomes but are reduced in hydrolytic enzymes transported by mannose-6-phosphate receptors (MPRs). We found that the effector SifA subverted Rab9-dependent retrograde trafficking of MPRs, thereby attenuating lysosome function. This required binding of SifA to its host cell target SKIP/PLEKHM2. Furthermore, SKIP regulated retrograde trafficking of MPRs in noninfected cells. Translocated SifA formed a stable complex with SKIP and Rab9 in infected cells. Sequestration of Rab9 by SifA-SKIP accounted for the effect of SifA on MPR transport and lysosome function. Growth of Salmonella increased in cells with reduced lysosomal activity and decreased in cells with higher lysosomal activity. These results suggest that Salmonella vacuoles undergo fusion with lysosomes whose potency has been reduced by SifA.

Original languageEnglish
Pages (from-to)963-967
Number of pages5
JournalScience
Volume338
Issue number6109
DOIs
Publication statusPublished - 16 Nov 2012

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