+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Diverting intracellular trafficking of Salmonella to the lysosome through activation of the late endocytic Rab7 by intracellular delivery of muramyl dipeptide



Diverting intracellular trafficking of Salmonella to the lysosome through activation of the late endocytic Rab7 by intracellular delivery of muramyl dipeptide



Journal of Cell Science 115(Pt 18): 3693-3701



Previously, we showed that live Salmonella-containing phagosomes (LSP) recruit early acting Rab5 and promote fusion with early endosomes, thus avoiding transport to the lysosomes. Therefore, live Salmonella survive in a specialized compartment. Here we show that scavenger-receptor-mediated intracellular delivery of muramyl dipeptide (MDP) to macrophages leads to efficient killing of Salmonella both in vitro and in vivo. To understand the intracellular trafficking modulation of Salmonella by delivery of MDP, we investigated the levels of endocytic Rab proteins, which are the major regulators of vesicular transport. Western blot analysis reveals reduced Rab5 and enhanced Rab7 content in the maleylated bovine serum albumin-MDP (MBSA-MDP)-treated cells. The reduced content of Rab5 in the treated cells and on phagosomes inhibits the fusion of Salmonella-containing phagosomes with early endosomes, and the enhanced Rab7 content in these cells facilitated targeting of LSP to lysosomes, which contain cathepsin D and vacuolar ATPase, for killing. In vitro reconstitution of lysosomal transport demonstrated that a reduced content of Rab5 and an enhanced level of Rab7 in MBSA-MDP-treated cells is primarily responsible for targeting Salmonella to lysosomes. Intracellular delivery of MDP thus offers a general strategy against macrophage-associated infections caused by intracellular pathogens that survive in the host cell by resisting transport to lysosomes.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 010488508

Download citation: RISBibTeXText

PMID: 12186955

DOI: 10.1242/jcs.00034


Related references

Pannexin-1-mediated intracellular delivery of muramyl dipeptide induces caspase-1 activation via cryopyrin/NLRP3 independently of Nod2. Journal of Immunology 180(6): 4050-4057, 2008

Improved intracellular delivery of a muramyl dipeptide analog by means of nanocapsules. International Journal of Immunopharmacology 16(5-6): 451-456, 1994

Stimulation of macrophage protease secretion via liposomal delivery of muramyl dipeptide derivatives to intracellular sites. Immunology 51(3): 517-527, 1984

The activation of tumoricidal properties of human blood monocytes by muramyl dipeptide requires specific intracellular interaction. Journal of Immunology 136(6): 2311-2317, 1986

Salmonella Disrupts Host Endocytic Trafficking by SopD2-Mediated Inhibition of Rab7. Cell Reports 12(9): 1508-1518, 2015

Intracellular trafficking during liver regeneration. Alterations in late endocytic and transcytotic pathways. Journal of Hepatology 40(1): 132-139, 2004

Understanding endocytic pathways and intracellular trafficking: a prerequisite for effective design of advanced drug delivery systems. Advanced Drug Delivery Reviews 55(11): 1353-1357, 2003

Trafficking from CD63-positive late endocytic multivesicular bodies is essential for intracellular development of Chlamydia trachomatis. Journal of Cell Science 119(Pt 2): 350-359, 2006

Leishmania RAB7: characterisation of terminal endocytic stages in an intracellular parasite. Molecular and Biochemical Parasitology 123(2): 105-113, 2002

Vps34 regulates Rab7 and late endocytic trafficking through recruitment of the GTPase-activating protein Armus. Journal of Cell Science 129(23): 4424-4435, 2016

Rab7 regulates late endocytic trafficking downstream of multivesicular body biogenesis and cargo sequestration. Journal of Biological Chemistry 284(18): 12110-12124, 2009

Late endosomal Rab7 regulates lysosomal trafficking of endocytic but not biosynthetic cargo in Trypanosoma brucei. Molecular Microbiology 82(3): 664-678, 2011

Clathrin- and dynamin-dependent endocytic pathway regulates muramyl dipeptide internalization and NOD2 activation. Journal of Immunology 182(7): 4321-4327, 2009

Modulation of the intracellular survival of Brucella abortus by tuftsin and muramyl dipeptide. Veterinary Immunology and Immunopathology 36(3): 265-279, 1993

Uptake of fluoresceinated muramyl dipeptide by alveolar macrophages suggests intracellular receptors. Journal of Allergy & Clinical Immunology 81(1): 171, 1988