Ralph R. Isberg

RNA Interference Analysis of Legionella in Drosophila Cells: Exploitation of Early Secretory Apparatus Dynamics (2006)

Marion S. Dorer, Donald Kirton, Joel S. Bader, Ralph R. Isberg

Legionella pneumophila translocates multiple bacterial effector proteins into host cells to direct formation of a replication vacuole for the bacterium. The emerging consensus is that formation of...

Yersinia pseudotuberculosis Spatially Controls Activation and Misregulation of Host Cell Rac1 (2005)

Ka-Wing Wong, Ralph R. Isberg

Yersinia pseudotuberculosis binds host cells and modulates the mammalian Rac1 guanosine triphosphatase (GTPase) at two levels. Activation of Rac1 results from integrin receptor engagement, while...

Involvement of focal adhesion kinase in invasin-mediated uptake

Alrutz, Michael A., Isberg, Ralph R.

High-efficiency entry of the enteropathogenic bacterium Yersinia pseudotuberculosis into nonphagocytic cells is mediated by the bacterial outer membrane protein invasin. Invasin-mediated uptake...

An Immunoglobulin Superfamily-Like Domain Unique to the Yersinia pseudotuberculosis Invasin Protein Is Required for Stimulation of Bacterial Uptake via Integrin Receptors

Dersch, Petra, Isberg, Ralph R.

The binding of the Yersinia pseudotuberculosis and Yersinia enterocolitica invasin proteins to β1 integrin receptors allows internalization of these organisms by cultured cells. The C-terminal...

Intracellular Growth of Legionella pneumophila in Dictyostelium discoideum, a System for Genetic Analysis of Host-Pathogen Interactions

Solomon, Jonathan M., Rupper, Adam, Cardelli, James A., Isberg, Ralph R.

Conditions were established in which Legionella pneumophila, an intracellular bacterial pathogen, could replicate within the unicellular organism Dictyostelium discoideum. By several criteria, L....

Identification of Linked Legionella pneumophila Genes Essential for Intracellular Growth and Evasion of the Endocytic Pathway

Andrews, Helene L., Vogel, Joseph P., Isberg, Ralph R.

Legionella pneumophila replicates within a specialized phagosome in cultured cells, a function necessary for its pathogenicity. The replicative phagosome lacks membrane marker proteins, such as the...

Macrophage-Induced Genes of Legionella pneumophila: Protection from Reactive Intermediates and Solute Imbalance during Intracellular Growth

Rankin, Susannah, Li, Zhiru, Isberg, Ralph R.

A promoter-probe strategy was devised to identify genes specifically expressed by Legionella pneumophila during growth within the macrophage. Random fragments from the L. pneumophila chromosome were...

Intracellular Replication of Mycobacterium marinum within Dictyostelium discoideum: Efficient Replication in the Absence of Host Coronin

Solomon, Jonathan M., Leung, Grace S., Isberg, Ralph R.

Mycobacterium marinum causes tuberculosis-like disease in fish and amphibians and has been used as a model mycobacterial species because of its rapid growth and less stringent containment...

Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer

Luo, Zhao-Qing, Isberg, Ralph R.

Legionella pneumophila is an intracellular pathogen that multiplies in a specialized vacuole within host cells. Biogenesis of this vacuole requires the Dot/Icm type IV protein translocation system....

Legionella pneumophila Replication Vacuole Formation Involves Rapid Recruitment of Proteins of the Early Secretory System

Derré, Isabelle, Isberg, Ralph R.

Legionella pneumophila vacuole biogenesis was analyzed by using a cell-free system. We show that calnexin, Sec22b, and Rab1 are recruited to the vacuole very shortly after bacterial uptake, and we...

IcmF and DotU Are Required for Optimal Effector Translocation and Trafficking of the Legionella pneumophila Vacuole

VanRheenen, Susan M., Duménil, Guillaume, Isberg, Ralph R.

The gram-negative bacterium Legionella pneumophila causes a severe form of pneumonia called Legionnaires' disease, characterized by bacterial replication within alveolar macrophages. Prior to...

Macrophages from Mice with the Restrictive Lgn1 Allele Exhibit Multifactorial Resistance to Legionella pneumophila

Derré, Isabelle, Isberg, Ralph R.

Although Legionella pneumophila can multiply in diverse cell types from a variety of species, macrophages from most inbred mouse strains are nonpermissive for intracellular replication and allow...

The DotL Protein, a Member of the TraG-Coupling Protein Family, Is Essential for Viability of Legionella pneumophila Strain Lp02

Buscher, Benjamin A., Conover, Gloria M., Miller, Jennifer L., Vogel, Sinae A., Meyers, Stacey N., Isberg, Ralph R., ...

Legionella pneumophila is able to survive inside phagocytic cells by an internalization route that bypasses fusion of the nascent phagosome with the endocytic pathway to allow formation of a...

Yersinia pseudotuberculosis Spatially Controls Activation and Misregulation of Host Cell Rac1

Wong, Ka-Wing, Isberg, Ralph R

Yersinia pseudotuberculosis binds host cells and modulates the mammalian Rac1 guanosine triphosphatase (GTPase) at two levels. Activation of Rac1 results from integrin receptor engagement, while...

LidA, a Translocated Substrate of the Legionella pneumophila Type IV Secretion System, Interferes with the Early Secretory Pathway

Derré, Isabelle, Isberg, Ralph R.

Legionella pneumophila uses a type IV secretion system to deliver effector molecules into the host cell and establish its replication vacuole. In this study, we investigated the role of LidA, a...

RNA Interference Analysis of Legionella in Drosophila Cells: Exploitation of Early Secretory Apparatus Dynamics

Dorer, Marion S, Kirton, Donald, Bader, Joel S, Isberg, Ralph R

Legionella pneumophila translocates multiple bacterial effector proteins into host cells to direct formation of a replication vacuole for the bacterium. The emerging consensus is that formation of...

Members of a Legionella pneumophila Family of Proteins with ExoU (Phospholipase A) Active Sites Are Translocated to Target Cells

VanRheenen, Susan M., Luo, Zhao-Qing, O'Connor, Tamara, Isberg, Ralph R.

Legionella pneumophila replicates within alveolar macrophages, causing a severe pneumonia termed Legionnaires' disease. The bacterium resides within a vacuole that escapes immediate transport to the...

Involvement of focal adhesion kinase in invasin-mediated uptake

Alrutz, Michael A., Isberg, Ralph R.

High-efficiency entry of the enteropathogenic bacterium Yersinia pseudotuberculosis into nonphagocytic cells is mediated by the bacterial outer membrane protein invasin. Invasin-mediated uptake...

An Immunoglobulin Superfamily-Like Domain Unique to the Yersinia pseudotuberculosis Invasin Protein Is Required for Stimulation of Bacterial Uptake via Integrin Receptors

Dersch, Petra, Isberg, Ralph R.

The binding of the Yersinia pseudotuberculosis and Yersinia enterocolitica invasin proteins to β1 integrin receptors allows internalization of these organisms by cultured cells. The C-terminal...

Intracellular Growth of Legionella pneumophila in Dictyostelium discoideum, a System for Genetic Analysis of Host-Pathogen Interactions

Solomon, Jonathan M., Rupper, Adam, Cardelli, James A., Isberg, Ralph R.

Conditions were established in which Legionella pneumophila, an intracellular bacterial pathogen, could replicate within the unicellular organism Dictyostelium discoideum. By several criteria, L....

Identification of Linked Legionella pneumophila Genes Essential for Intracellular Growth and Evasion of the Endocytic Pathway

Andrews, Helene L., Vogel, Joseph P., Isberg, Ralph R.

Legionella pneumophila replicates within a specialized phagosome in cultured cells, a function necessary for its pathogenicity. The replicative phagosome lacks membrane marker proteins, such as the...

Macrophage-Induced Genes of Legionella pneumophila: Protection from Reactive Intermediates and Solute Imbalance during Intracellular Growth

Rankin, Susannah, Li, Zhiru, Isberg, Ralph R.

A promoter-probe strategy was devised to identify genes specifically expressed by Legionella pneumophila during growth within the macrophage. Random fragments from the L. pneumophila chromosome were...

Intracellular Replication of Mycobacterium marinum within Dictyostelium discoideum: Efficient Replication in the Absence of Host Coronin

Solomon, Jonathan M., Leung, Grace S., Isberg, Ralph R.

Mycobacterium marinum causes tuberculosis-like disease in fish and amphibians and has been used as a model mycobacterial species because of its rapid growth and less stringent containment...

Multiple substrates of the Legionella pneumophila Dot/Icm system identified by interbacterial protein transfer

Luo, Zhao-Qing, Isberg, Ralph R.

Legionella pneumophila is an intracellular pathogen that multiplies in a specialized vacuole within host cells. Biogenesis of this vacuole requires the Dot/Icm type IV protein translocation system....

Legionella pneumophila Replication Vacuole Formation Involves Rapid Recruitment of Proteins of the Early Secretory System

Derré, Isabelle, Isberg, Ralph R.

Legionella pneumophila vacuole biogenesis was analyzed by using a cell-free system. We show that calnexin, Sec22b, and Rab1 are recruited to the vacuole very shortly after bacterial uptake, and we...

IcmF and DotU Are Required for Optimal Effector Translocation and Trafficking of the Legionella pneumophila Vacuole

VanRheenen, Susan M., Duménil, Guillaume, Isberg, Ralph R.

The gram-negative bacterium Legionella pneumophila causes a severe form of pneumonia called Legionnaires' disease, characterized by bacterial replication within alveolar macrophages. Prior to...

Macrophages from Mice with the Restrictive Lgn1 Allele Exhibit Multifactorial Resistance to Legionella pneumophila

Derré, Isabelle, Isberg, Ralph R.

Although Legionella pneumophila can multiply in diverse cell types from a variety of species, macrophages from most inbred mouse strains are nonpermissive for intracellular replication and allow...

The DotL Protein, a Member of the TraG-Coupling Protein Family, Is Essential for Viability of Legionella pneumophila Strain Lp02

Buscher, Benjamin A., Conover, Gloria M., Miller, Jennifer L., Vogel, Sinae A., Meyers, Stacey N., Isberg, Ralph R., ...

Legionella pneumophila is able to survive inside phagocytic cells by an internalization route that bypasses fusion of the nascent phagosome with the endocytic pathway to allow formation of a...

LidA, a Translocated Substrate of the Legionella pneumophila Type IV Secretion System, Interferes with the Early Secretory Pathway

Derré, Isabelle, Isberg, Ralph R.

Legionella pneumophila uses a type IV secretion system to deliver effector molecules into the host cell and establish its replication vacuole. In this study, we investigated the role of LidA, a...

Yersinia pseudotuberculosis Spatially Controls Activation and Misregulation of Host Cell Rac1

Wong, Ka-Wing, Isberg, Ralph R

Yersinia pseudotuberculosis binds host cells and modulates the mammalian Rac1 guanosine triphosphatase (GTPase) at two levels. Activation of Rac1 results from integrin receptor engagement, while...

RNA Interference Analysis of Legionella in Drosophila Cells: Exploitation of Early Secretory Apparatus Dynamics

Dorer, Marion S, Kirton, Donald, Bader, Joel S, Isberg, Ralph R

Legionella pneumophila translocates multiple bacterial effector proteins into host cells to direct formation of a replication vacuole for the bacterium. The emerging consensus is that formation of...

Members of a Legionella pneumophila Family of Proteins with ExoU (Phospholipase A) Active Sites Are Translocated to Target Cells

VanRheenen, Susan M., Luo, Zhao-Qing, O'Connor, Tamara, Isberg, Ralph R.

Legionella pneumophila replicates within alveolar macrophages, causing a severe pneumonia termed Legionnaires' disease. The bacterium resides within a vacuole that escapes immediate transport to the...

A Legionella pneumophila-translocated substrate that is required for growth within macrophages and protection from host cell death

Laguna, Rita K., Creasey, Elizabeth A., Li, Zhiru, Valtz, Nicole, Isberg, Ralph R.

Legionella pneumophila requires the Dot/Icm protein translocation system to replicate within host cells as a critical component of Legionnaire's pneumonia. None of the known individual substrates of...

Growth of Yersinia pseudotuberculosis in Mice Occurs Independently of Toll-Like Receptor 2 Expression and Induction of Interleukin-10▿

Auerbuch, Victoria, Isberg, Ralph R.

Pathogenic Yersinia translocates effector proteins into target cells via a type III secretion system (TTSS), modulating the host immune response. A component of the TTSS translocon, LcrV, has been...

Yersinia pseudotuberculosis disseminates directly from a replicating bacterial pool in the intestine

Barnes, Penelope D., Bergman, Molly A., Mecsas, Joan, Isberg, Ralph R.

Dissemination of Yersinia pseudotuberculosis within mice after oral inoculation was analyzed. Y. pseudotuberculosis translocated to organs such as the liver and spleen shortly after oral inoculation,...

NF-κB translocation prevents host cell death after low-dose challenge by Legionella pneumophila

Losick, Vicki P., Isberg, Ralph R.

Legionella pneumophila, the causative agent of Legionnaires' disease, grows within macrophages and manipulates target cell signaling. Formation of a Legionella-containing replication vacuole requires...

Arf6 and Phosphoinositol-4-Phosphate-5-Kinase Activities Permit Bypass of the Rac1 Requirement for β1 Integrin–mediated Bacterial Uptake

Wong, Ka-Wing, Isberg, Ralph R.

Efficient entry of the bacterium Yersinia pseudotuberculosis into mammalian cells requires the binding of the bacterial invasin protein to β1 integrin receptors and the activation of the small...

Legionella pneumophila Is Internalized by a Macropinocytotic Uptake Pathway Controlled by the Dot/Icm System and the Mouse Lgn1 Locus✪

Watarai, Masahisa, Derre, Isabelle, Kirby, James, Growney, Joseph D., Dietrich, William F., Isberg, Ralph R.

The products of the Legionella pneumophila dot/icm genes enable the bacterium to replicate within a macrophage vacuole. This study demonstrates that the Dot/Icm machinery promotes macropinocytotic...

Distinct Roles for MyD88 and Toll-Like Receptors 2, 5, and 9 in Phagocytosis of Borrelia burgdorferi and Cytokine Induction ▿

Shin, Ok S., Isberg, Ralph R., Akira, Shizuo, Uematsu, Satoshi, Behera, Aruna K., Hu, Linden T.

The contribution of Toll-like receptors (TLRs) to phagocytosis of Borrelia burgdorferi has not been extensively studied. We show that bone marrow-derived macrophages (BMDM) from MyD88−/− mice or...

The Polybasic Region of Rac1 Modulates Bacterial Uptake Independently of Self-association and Membrane Targeting*

Wong, Ka-Wing, Mohammadi, Sina, Isberg, Ralph R.

The COOH-terminal polybasic region (PBR) of Rac1, a Rho family GTPase member, is required for Rac1 self-association, membrane localization, nuclear translocation, and interaction with downstream...

A Hemidominant Naip5 Allele in Mouse Strain MOLF/Ei-Derived Macrophages Restricts Legionella pneumophila Intracellular Growth ▿

Losick, Vicki P., Stephan, Kristin, Smirnova, Irina I., Isberg, Ralph R., Poltorak, Alexander

Mouse-derived macrophages have the unique ability to restrict or permit Legionella pneumophila intracellular growth. The common inbred mouse strain C57BL/6J (B6) restricts L. pneumophila growth,...

CD8+ T Cells Restrict Yersinia pseudotuberculosis Infection: Bypass of Anti-Phagocytosis by Targeting Antigen-Presenting Cells

Bergman, Molly A., Loomis, Wendy P., Mecsas, Joan, Starnbach, Michael N., Isberg, Ralph R.

All Yersinia species target and bind to phagocytic cells, but uptake and destruction of bacteria are prevented by injection of anti-phagocytic Yop proteins into the host cell. Here we provide...