Trafficking of the Salmonella Vacuole in Macrophages

Salmonella enterica is a facultative intracellular pathogen which can replicate in macrophages. Intracellular Salmonella exist in a membrane‐bound compartment called the Salmonella‐containing vacuole. Most studies on Salmonella trafficking in relation to the endocytic pathway have concluded that the majority of Salmonella‐containing vacuoles do not interact extensively with late endosomes and lysosomes. Numerous bacterial genes have been identified which are required for survival and replication in macrophages. These include the spv operon, located on the large virulence plasmid, the phoP‐phoQ regulon, and those connected with the Salmonella pathogenicity island 2 type III secretion system. The functions of some of these genes are beginning to be understood. In this review, I discuss their roles in relation to our broader understanding of Salmonella trafficking in macrophages.

[1]  W. Hardt,et al.  Identification of SopE2 from Salmonella typhimurium, a conserved guanine nucleotide exchange factor for Cdc42 of the host cell , 2000, Molecular microbiology.

[2]  M. Horwitz,et al.  The Mycobacterium tuberculosis phagosome interacts with early endosomes and is accessible to exogenously administered transferrin , 1996, The Journal of experimental medicine.

[3]  G. Arenas,et al.  Intracellular Trafficking of Brucella abortus in J774 Macrophages , 2000, Infection and Immunity.

[4]  S. Méresse,et al.  Salmonella maintains the integrity of its intracellular vacuole through the action of SifA , 2000, The EMBO journal.

[5]  M. Roberts,et al.  The alternative sigma factor, sigmaE, is critically important for the virulence of Salmonella typhimurium. , 1999, Infection and immunity.

[6]  M. Horwitz.  The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes , 1983, The Journal of experimental medicine.

[7]  U. Schaible,et al.  Mycobacterium‐containing phagosomes are accessible to early endosomes and reflect a transitional state in normal phagosome biogenesis. , 1996, The EMBO journal.

[8]  S. Zeronian,et al.  The accessibility of cellulose as determined by dye adsorption , 1996 .

[9]  Sjaak van Voorden,et al.  Novel Salmonella enterica Serovar Typhimurium Protein That Is Indispensable for Virulence and Intracellular Replication , 2001, Infection and Immunity.

[10]  F. Heffron,et al.  Salmonella Pathogenicity Island 1-Independent Induction of Apoptosis in Infected Macrophages bySalmonella enterica Serotype Typhimurium , 2000, Infection and Immunity.

[11]  Y. Kikuchi,et al.  Use of confocal microscopy to detect Salmonella typhimurium within host cells associated with Spv-mediated intracellular proliferation. , 2000, Microbial pathogenesis.

[12]  M. Stein,et al.  Aggregation of host endosomes by Salmonella requires SPI2 translocation of SseFG and involves SpvR and the fms–aroE intragenic region , 2000, Molecular microbiology.

[13]  J. Shea,et al.  Genes encoding putative effector proteins of the type III secretion system of Salmonella pathogenicity island 2 are required for bacterial virulence and proliferation in macrophages , 1998, Molecular microbiology.

[14]  J. Shea,et al.  Identification of a virulence locus encoding a second type III secretion system in Salmonella typhimurium. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  E. Groisman,et al.  Mg2+ as an Extracellular Signal: Environmental Regulation of Salmonella Virulence , 1996, Cell.

[16]  M. Hensel,et al.  Regulation of virulence genes by environmental signals in Salmonella typhimurium , 1999, Electrophoresis.

[17]  S. Libby,et al.  Dynamics of growth and death within a Salmonella typhimurium population during infection of macrophages. , 1997, Canadian journal of microbiology.

[18]  M. Swanson,et al.  Evidence that Dot‐dependent and ‐independent factors isolate the Legionella pneumophila phagosome from the endocytic network in mouse macrophages , 2001, Cellular microbiology.

[19]  F. Heffron,et al.  Salmonella typhimurium loci involved in survival within macrophages , 1994, Infection and immunity.

[20]  F. Koch-Nolte,et al.  Actin is ADP‐ribosylated by the Salmonella enterica virulence‐associated protein SpvB , 2001, Molecular microbiology.

[21]  T. Wallis,et al.  Salmonella enterica Serovars Typhimurium and Dublin Can Lyse Macrophages by a Mechanism Distinct from Apoptosis , 2000, Infection and Immunity.

[22]  C. Rosenberger,et al.  SifA permits survival and replication of Salmonella typhimurium in murine macrophages , 2001, Cellular microbiology.

[23]  F. Fang,et al.  SlyA, a transcriptional regulator of Salmonella typhimurium, is required for resistance to oxidative stress and is expressed in the intracellular environment of macrophages , 1997, Infection and immunity.

[24]  P. Gulig,et al.  The Salmonella typhimurium virulence plasmid increases the growth rate of salmonellae in mice , 1993, Infection and immunity.

[25]  V. Aber,et al.  Phagolysosome formation, cyclic adenosine 3':5'-monophosphate and the fate of Salmonella typhimurium within mouse peritoneal macrophages. , 1979, Journal of general microbiology.

[26]  S. Falkow,et al.  OmpR Regulates the Two-Component System SsrA-SsrB in Salmonella Pathogenicity Island 2 , 2000, Journal of bacteriology.

[27]  J. Galán,et al.  Supramolecular structure of the Salmonella typhimurium type III protein secretion system. , 1998, Science.

[28]  Samuel I. Miller,et al.  SseBCD Proteins Are Secreted by the Type III Secretion System of Salmonella Pathogenicity Island 2 and Function as a Translocon , 2001, Journal of bacteriology.

[29]  J. Galán,et al.  A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion , 1999, Nature.

[30]  Eduardo A. Groisman,et al.  The Pleiotropic Two-Component Regulatory System PhoP-PhoQ , 2001, Journal of bacteriology.

[31]  J. Galán,et al.  Salmonella spp. are cytotoxic for cultured macrophages , 1996, Molecular microbiology.

[32]  M. Pallen,et al.  A novel EspA‐associated surface organelle of enteropathogenic Escherichia coli involved in protein translocation into epithelial cells , 1998, The EMBO journal.

[33]  S. Miller,et al.  Characterization of the Salmonella typhimurium pagC/pagD chromosomal region , 1995, Journal of bacteriology.

[34]  T. Arai,et al.  Specific inhibition of phagosome-lysosome fusion in murine macrophages mediated by Salmonella typhimurium infection. , 1990, FEMS microbiology immunology.

[35]  S. Falkow,et al.  Bacterial genetics by flow cytometry: rapid isolation of Salmonella typhimurium acid‐inducible promoters by differential fluorescence induction , 1996, Molecular microbiology.

[36]  W. Nauseef,et al.  Salmonella Pathogenicity Island 2-Encoded Type III Secretion System Mediates Exclusion of NADPH Oxidase Assembly from the Phagosomal Membrane1 , 2001, The Journal of Immunology.

[37]  J. Gorvel,et al.  The rab7 GTPase controls the maturation of Salmonella typhimurium‐containing vacuoles in HeLa cells , 1999, The EMBO journal.

[38]  B. Finlay,et al.  Biogenesis of Salmonella typhimurium‐containing vacuoles in epithelial cells involves interactions with the early endocytic pathway , 1999, Cellular microbiology.

[39]  C. Sasakawa,et al.  Supermolecular structure of the enteropathogenic Escherichia coli type III secretion system and its direct interaction with the EspA-sheath-like structure , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[40]  J. Pfeifer,et al.  The phoP locus influences processing and presentation of Salmonella typhimurium antigens by activated macrophages , 1995, Molecular microbiology.

[41]  C. Beuzón,et al.  A role for the PhoP/Q regulon in inhibition of fusion between lysosomes and Salmonella‐containing vacuoles in macrophages , 2001, Cellular microbiology.

[42]  N. Reiner,et al.  The Salmonella spvB virulence gene encodes an enzyme that ADP‐ribosylates actin and destabilizes the cytoskeleton of eukaryotic cells , 2001, Molecular microbiology.

[43]  M. Raje,et al.  Live Salmonella Modulate Expression of Rab Proteins to Persist in a Specialized Compartment and Escape Transport to Lysosomes* , 2000, The Journal of Biological Chemistry.

[44]  S. Miller,et al.  Identification of PhoP-PhoQ activated genes within a duplicated region of the Salmonella typhimurium chromosome. , 1998, Microbial pathogenesis.

[45]  M. Baldeón,et al.  Expression of constitutively active Rab5 uncouples maturation of the Salmonella‐containing vacuole from intracellular replication , 2001, Cellular microbiology.

[46]  J. R. Klein,et al.  Salmonella Pathogenicity Island 2-Encoded Proteins SseC and SseD Are Essential for Virulence and Are Substrates of the Type III Secretion System , 2001, Infection and Immunity.

[47]  G. Cornelis,et al.  Assembly and function of type III secretory systems. , 2000, Annual review of microbiology.

[48]  M. Raje,et al.  Live Salmonella Recruits N-Ethylmaleimide–Sensitive Fusion Protein on Phagosomal Membrane and Promotes Fusion with Early Endosome , 2000, The Journal of cell biology.

[49]  J. Shea,et al.  Influence of the Salmonella typhimuriumPathogenicity Island 2 Type III Secretion System on Bacterial Growth in the Mouse , 1999, Infection and Immunity.

[50]  F. Fang,et al.  Salmonella pathogenicity island 2-dependent evasion of the phagocyte NADPH oxidase. , 2000, Science.

[51]  S. Falkow,et al.  Acidification of phagosomes containing Salmonella typhimurium in murine macrophages , 1996, Infection and immunity.

[52]  M. Martínez-Lorenzo,et al.  Remodelling of the actin cytoskeleton is essential for replication of intravacuolar Salmonella , 2001, Cellular microbiology.

[53]  L. Hernandez,et al.  A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization , 2001, Molecular microbiology.

[54]  H. Ochman,et al.  Identification of a pathogenicity island required for Salmonella survival in host cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[55]  Sezgin Erdoğan,et al.  Environmental regulation of Salmonella pathogenicity island 2 gene expression , 1999, Molecular microbiology.

[56]  C. Haidaris,et al.  Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[57]  B. Finlay,et al.  Identification of a Salmonella virulence gene required for formation of filamentous structures containing lysosomal membrane glycoproteins within epithelial cells , 1996, Molecular microbiology.

[58]  G. Cornelis,et al.  Translocation of a hybrid YopE‐adenylate cyclase from Yersinia enterocolitica into HeLa cells , 1994, Molecular microbiology.

[59]  B. Finlay,et al.  Targeting of Salmonella typhimurium to vesicles containing lysosomal membrane glycoproteins bypasses compartments with mannose 6-phosphate receptors , 1995, The Journal of cell biology.

[60]  B. Finlay,et al.  Murine Salmonellosis Studied by Confocal Microscopy: Salmonella typhimurium Resides Intracellularly Inside Macrophages and Exerts a Cytotoxic Effect on Phagocytes In Vivo , 1997, The Journal of experimental medicine.

[61]  S. Miller,et al.  Salmonella typhimurium activates virulence gene transcription within acidified macrophage phagosomes. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[62]  S. Falkow,et al.  Salmonella Exploits Caspase-1 to Colonize Peyer's Patches in a Murine Typhoid Model , 2000, The Journal of experimental medicine.

[63]  Etienne Gagnon,et al.  The Phagosome Proteome: Insight into Phagosome Functions , 2001 .

[64]  F. Heffron,et al.  Salmonella SsrB activates a global regulon of horizontally acquired genes , 2000, Molecular microbiology.

[65]  G. Griffiths,et al.  Involvement of ezrin/moesin in de novo actin assembly on phagosomal membranes , 2000, The EMBO journal.

[66]  F. Heffron,et al.  Inhibition of macrophage phagosome-lysosome fusion by Salmonella typhimurium , 1991, Infection and immunity.

[67]  P. Majerus,et al.  SopB, a protein required for virulence of Salmonella dublin, is an inositol phosphate phosphatase. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[68]  C. Hueck,et al.  Type III Protein Secretion Systems in Bacterial Pathogens of Animals and Plants , 1998, Microbiology and Molecular Biology Reviews.

[69]  F. Heffron,et al.  Induction of Salmonella stress proteins upon infection of macrophages. , 1990, Science.

[70]  S. Falkow,et al.  Functional analysis of ssaJ and the ssaK/U operon, 13 genes encoding components of the type III secretion apparatus of Salmonella Pathogenicity Island 2 , 1997, Molecular microbiology.

[71]  S. Miller,et al.  Rapid and complete fusion of macrophage lysosomes with phagosomes containing Salmonella typhimurium , 1996, Infection and immunity.

[72]  E. Groisman,et al.  The Salmonella selC locus contains a pathogenicity island mediating intramacrophage survival , 1997, The EMBO journal.

[73]  G. Fantuzzi,et al.  Defective localization of the NADPH phagocyte oxidase to Salmonella-containing phagosomes in tumor necrosis factor p55 receptor-deficient macrophages , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[74]  B. Finlay,et al.  Salmonella induces the formation of filamentous structures containing lysosomal membrane glycoproteins in epithelial cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[75]  S. Falkow,et al.  The unique trafficking pattern of Salmonella typhimurium-containing phagosomes in murine macrophages is independent of the mechanism of bacterial entry , 1997, Infection and immunity.

[76]  M. Hensel,et al.  pH‐dependent secretion of SseB, a product of the SPI‐2 type III secretion system of Salmonella typhimurium , 1999, Molecular microbiology.

[77]  S Falkow,et al.  Fluorescence-based isolation of bacterial genes expressed within host cells. , 1997, Science.

[78]  B. Finlay,et al.  Salmonella typhimurium Virulence Genes Are Induced upon Bacterial Invasion into Phagocytic and Nonphagocytic Cells , 1999, Infection and Immunity.

[79]  J. Shea,et al.  Simultaneous identification of bacterial virulence genes by negative selection. , 1995, Science.

[80]  Xiao-Zhe Huang,et al.  Differential Bacterial Survival, Replication, and Apoptosis-Inducing Ability of Salmonella Serovars within Human and Murine Macrophages , 2000, Infection and Immunity.

[81]  M. Roberts,et al.  The Alternative Sigma Factor, ςE, Is Critically Important for the Virulence of Salmonella typhimurium , 1999, Infection and Immunity.

[82]  F. Heffron,et al.  Role of Salmonella typhimurium Mn-superoxide dismutase (SodA) in protection against early killing by J774 macrophages , 1995, Infection and immunity.

[83]  Jonathan D. Cohen,et al.  Intracellular replication of Salmonella typhimurium strains in specific subsets of splenic macrophages in vivo , 2001, Cellular microbiology.

[84]  S. Miller,et al.  A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[85]  E. Groisman,et al.  A Salmonella virulence protein that inhibits cellular trafficking , 1999, The EMBO journal.

[86]  K. Schuebel,et al.  S. typhimurium Encodes an Activator of Rho GTPases that Induces Membrane Ruffling and Nuclear Responses in Host Cells , 1998, Cell.

[87]  S Falkow,et al.  Macrophage‐dependent induction of the Salmonella pathogenicity island 2 type III secretion system and its role in intracellular survival , 1998, Molecular microbiology.

[88]  S. Miller,et al.  A conserved amino acid sequence directing intracellular type III secretion by Salmonella typhimurium. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[89]  B. Cookson,et al.  Salmonella induces macrophage death by caspase‐1‐dependent necrosis , 2000, Molecular microbiology.

[90]  J. Liautard,et al.  Brucella suis-Impaired Specific Recognition of Phagosomes by Lysosomes due to Phagosomal Membrane Modifications , 2001, Infection and Immunity.