Daniel A. Portnoy

Distinct TLR- and NLR-Mediated Transcriptional Responses to an Intracellular Pathogen (2008)

Jess H. Leber, Gregory T. Crimmins, Sridharan Raghavan, Jeffery S. Cox, Daniel A. Portnoy

How the innate immune system tailors specific responses to diverse microbial infections is not well understood. Cells use a limited number of host receptors and signaling pathways to both...

Listeriolysin O Secreted by Listeria monocytogenes into the Host Cell Cytosol Is Degraded by the N-End Rule Pathway (2007)

Schnupf, Pamela, Zhou, Jianmin, Varshavsky, Alexander, Portnoy, Daniel A.

The intracellular pathogen Listeria monocytogenes escapes from a phagosomal compartment into the cytosol by secreting the pore-forming cytolysin listeriolysin O (LLO). During the proliferation of L....

Bacterial Ligands Generated in a Phagosome Are Targets of the Cytosolic Innate Immune System (2007)

Anat A. Herskovits, Victoria Auerbuch, Daniel A. Portnoy

Macrophages are permissive hosts to intracellular pathogens, but upon activation become microbiocidal effectors of innate and cell-mediated immunity. How the fate of internalized microorganisms is...

Listeria monocytogenes Traffics from Maternal Organs to the Placenta and Back (2006)

Anna I. Bakardjiev, Julie A. Theriot, Daniel A. Portnoy

Infection with Listeria monocytogenes is a significant health problem during pregnancy. This study evaluates the role of trafficking between maternal organs and placenta in a pregnant guinea pig...

Expression of Listeriolysin O and ActA by Intracellular and Extracellular Listeria monocytogenes

Moors, Marlena A., Levitt, Brian, Youngman, Philip, Portnoy, Daniel A.

Listeria monocytogenes requires listeriolysin O (LLO) and ActA, the products of hly and actA, respectively, to establish a productive intracellular infection. LLO is essential for vacuolar lysis and...

Role of Listeriolysin O in Cell-to-Cell Spread of Listeria monocytogenes

Gedde, Margaret M., Higgins, Darren E., Tilney, Lewis G., Portnoy, Daniel A.

Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from a host vacuolar compartment and grows rapidly in the cytosol. Listeriolysin O (LLO) is a secreted...

Development of a Competitive Index Assay To Evaluate the Virulence of Listeria monocytogenes actA Mutants during Primary and Secondary Infection of Mice

Auerbuch, Victoria, Lenz, Laurel L., Portnoy, Daniel A.

We developed a competitive index assay for murine listeriosis that tests the virulence of Listeria monocytogenes strains in different organs and at various times postinoculation. Studies presented...

Pathogenicity and Immunogenicity of a Listeria monocytogenes Strain That Requires d-Alanine for Growth

Thompson, Robert J., Bouwer, H. G. Archie, Portnoy, Daniel A., Frankel, Fred R.

Listeria monocytogenes is an intracellular bacterial pathogen that elicits a strong cellular immune response following infection and therefore has potential use as a vaccine vector. However, while...

Innate recognition of bacteria by a macrophage cytosolic surveillance pathway

O'Riordan, Mary, Yi, Caroline H., Gonzales, Ramona, Lee, Kyung-Dall, Portnoy, Daniel A.

Host recognition of bacterial pathogens is a critical component of the immune response. Intracellular bacterial pathogens are able to evade the humoral immune system by residing within the host cell....

Construction, Characterization, and Use of Two Listeria monocytogenes Site-Specific Phage Integration Vectors

Lauer, Peter, Chow, Man Yin Nora, Loessner, Martin J., Portnoy, Daniel A., Calendar, Richard

Two site-specific shuttle integration vectors were developed with two different chromosomal bacteriophage integration sites to facilitate strain construction in Listeria monocytogenes. The first...

Inducible Control of Virulence Gene Expression in Listeria monocytogenes: Temporal Requirement of Listeriolysin O during Intracellular Infection

Dancz, Christina E., Haraga, Andrea, Portnoy, Daniel A., Higgins, Darren E.

We have constructed a lac repressor/operator-based system to tightly regulate expression of bacterial genes during intracellular infection by Listeria monocytogenes. An L. monocytogenes strain was...

SecA2-dependent secretion of autolytic enzymes promotes Listeria monocytogenes pathogenesis

Lenz, Laurel L., Mohammadi, Sina, Geissler, Aimee, Portnoy, Daniel A.

Pathogenic bacteria secrete proteins that promote invasion of host tissues and resistance to immune responses. However, secretion mechanisms that contribute to the enormous morbidity and mortality of...

Listeria monocytogenes Mutants That Fail To Compartmentalize Listerolysin O Activity Are Cytotoxic, Avirulent, and Unable To Evade Host Extracellular Defenses

Glomski, Ian J., Decatur, Amy L., Portnoy, Daniel A.

Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from a phagosome and grows in the host cell cytosol. Escape of the bacterium from the phagosome to the cytosol is...

Listeriosis in the Pregnant Guinea Pig: a Model of Vertical Transmission

Bakardjiev, Anna I., Stacy, Brian A., Fisher, Susan J., Portnoy, Daniel A.

Feto-placental infections represent a major cause of pregnancy complications, and yet the underlying molecular and cellular mechanisms of vertical transmission are poorly understood. Listeria...

A specific gene expression program triggered by Gram-positive bacteria in the cytosol

McCaffrey, Ramona L., Fawcett, Paul, O'Riordan, Mary, Lee, Kyung-Dall, Havell, Edward A., Brown, Patrick O., ...

Innate and adaptive immunity depends critically on host recognition of pathogen-associated molecules. Toll-like receptors (TLRs) are key mediators of pathogen surveillance at the cell or phagocytic...

Listeria-based cancer vaccines that segregate immunogenicity from toxicity

Brockstedt, Dirk G., Giedlin, Martin A., Leong, Meredith L., Bahjat, Keith S., Gao, Yi, Luckett, William, ...

The facultative intracellular bacterium Listeria monocytogenes is being developed as a cancer vaccine platform because of its ability to induce potent innate and adaptive immunity. For successful...

Use of RNA interference in Drosophila S2 cells to identify host pathways controlling compartmentalization of an intracellular pathogen

Cheng, Luisa W., Viala, Julie P. M., Stuurman, Nico, Wiedemann, Ursula, Vale, Ronald D., Portnoy, Daniel A.

Three genome-wide RNA interference screens were performed in Drosophila S2 cells to dissect the contribution of host processes to Listeria monocytogenes entry, vacuolar escape, and intracellular...

Listeria monocytogenes Traffics from Maternal Organs to the Placenta and Back

Bakardjiev, Anna I, Theriot, Julie A, Portnoy, Daniel A

Infection with Listeria monocytogenes is a significant health problem during pregnancy. This study evaluates the role of trafficking between maternal organs and placenta in a pregnant guinea pig...

Expression of Listeriolysin O and ActA by Intracellular and Extracellular Listeria monocytogenes

Moors, Marlena A., Levitt, Brian, Youngman, Philip, Portnoy, Daniel A.

Listeria monocytogenes requires listeriolysin O (LLO) and ActA, the products of hly and actA, respectively, to establish a productive intracellular infection. LLO is essential for vacuolar lysis and...

Role of Listeriolysin O in Cell-to-Cell Spread of Listeria monocytogenes

Gedde, Margaret M., Higgins, Darren E., Tilney, Lewis G., Portnoy, Daniel A.

Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from a host vacuolar compartment and grows rapidly in the cytosol. Listeriolysin O (LLO) is a secreted...

Development of a Competitive Index Assay To Evaluate the Virulence of Listeria monocytogenes actA Mutants during Primary and Secondary Infection of Mice

Auerbuch, Victoria, Lenz, Laurel L., Portnoy, Daniel A.

We developed a competitive index assay for murine listeriosis that tests the virulence of Listeria monocytogenes strains in different organs and at various times postinoculation. Studies presented...

Pathogenicity and Immunogenicity of a Listeria monocytogenes Strain That Requires d-Alanine for Growth

Thompson, Robert J., Bouwer, H. G. Archie, Portnoy, Daniel A., Frankel, Fred R.

Listeria monocytogenes is an intracellular bacterial pathogen that elicits a strong cellular immune response following infection and therefore has potential use as a vaccine vector. However, while...

Innate recognition of bacteria by a macrophage cytosolic surveillance pathway

O'Riordan, Mary, Yi, Caroline H., Gonzales, Ramona, Lee, Kyung-Dall, Portnoy, Daniel A.

Host recognition of bacterial pathogens is a critical component of the immune response. Intracellular bacterial pathogens are able to evade the humoral immune system by residing within the host cell....

Construction, Characterization, and Use of Two Listeria monocytogenes Site-Specific Phage Integration Vectors

Lauer, Peter, Chow, Man Yin Nora, Loessner, Martin J., Portnoy, Daniel A., Calendar, Richard

Two site-specific shuttle integration vectors were developed with two different chromosomal bacteriophage integration sites to facilitate strain construction in Listeria monocytogenes. The first...

Inducible Control of Virulence Gene Expression in Listeria monocytogenes: Temporal Requirement of Listeriolysin O during Intracellular Infection

Dancz, Christina E., Haraga, Andrea, Portnoy, Daniel A., Higgins, Darren E.

We have constructed a lac repressor/operator-based system to tightly regulate expression of bacterial genes during intracellular infection by Listeria monocytogenes. An L. monocytogenes strain was...

SecA2-dependent secretion of autolytic enzymes promotes Listeria monocytogenes pathogenesis

Lenz, Laurel L., Mohammadi, Sina, Geissler, Aimee, Portnoy, Daniel A.

Pathogenic bacteria secrete proteins that promote invasion of host tissues and resistance to immune responses. However, secretion mechanisms that contribute to the enormous morbidity and mortality of...

Listeria monocytogenes Mutants That Fail To Compartmentalize Listerolysin O Activity Are Cytotoxic, Avirulent, and Unable To Evade Host Extracellular Defenses

Glomski, Ian J., Decatur, Amy L., Portnoy, Daniel A.

Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from a phagosome and grows in the host cell cytosol. Escape of the bacterium from the phagosome to the cytosol is...

Listeriosis in the Pregnant Guinea Pig: a Model of Vertical Transmission

Bakardjiev, Anna I., Stacy, Brian A., Fisher, Susan J., Portnoy, Daniel A.

Feto-placental infections represent a major cause of pregnancy complications, and yet the underlying molecular and cellular mechanisms of vertical transmission are poorly understood. Listeria...

A specific gene expression program triggered by Gram-positive bacteria in the cytosol

McCaffrey, Ramona L., Fawcett, Paul, O'Riordan, Mary, Lee, Kyung-Dall, Havell, Edward A., Brown, Patrick O., ...

Innate and adaptive immunity depends critically on host recognition of pathogen-associated molecules. Toll-like receptors (TLRs) are key mediators of pathogen surveillance at the cell or phagocytic...

Listeria-based cancer vaccines that segregate immunogenicity from toxicity

Brockstedt, Dirk G., Giedlin, Martin A., Leong, Meredith L., Bahjat, Keith S., Gao, Yi, Luckett, William, ...

The facultative intracellular bacterium Listeria monocytogenes is being developed as a cancer vaccine platform because of its ability to induce potent innate and adaptive immunity. For successful...

Use of RNA interference in Drosophila S2 cells to identify host pathways controlling compartmentalization of an intracellular pathogen

Cheng, Luisa W., Viala, Julie P. M., Stuurman, Nico, Wiedemann, Ursula, Vale, Ronald D., Portnoy, Daniel A.

Three genome-wide RNA interference screens were performed in Drosophila S2 cells to dissect the contribution of host processes to Listeria monocytogenes entry, vacuolar escape, and intracellular...

Listeria monocytogenes Traffics from Maternal Organs to the Placenta and Back

Bakardjiev, Anna I, Theriot, Julie A, Portnoy, Daniel A

Infection with Listeria monocytogenes is a significant health problem during pregnancy. This study evaluates the role of trafficking between maternal organs and placenta in a pregnant guinea pig...

Cytosolic Entry Controls CD8+-T-Cell Potency during Bacterial Infection▿

Bahjat, Keith S., Liu, Weiqun, Lemmens, Edward E., Schoenberger, Stephen P., Portnoy, Daniel A., Dubensky, Thomas W., ...

Interaction with host immunoreceptors during microbial infection directly impacts the magnitude of the ensuing innate immune response. How these signals affect the quality of the adaptive T-cell...

Bacterial Ligands Generated in a Phagosome Are Targets of the Cytosolic Innate Immune System

Herskovits, Anat A, Auerbuch, Victoria, Portnoy, Daniel A

Macrophages are permissive hosts to intracellular pathogens, but upon activation become microbiocidal effectors of innate and cell-mediated immunity. How the fate of internalized microorganisms is...

Listeriolysin O Secreted by Listeria monocytogenes into the Host Cell Cytosol Is Degraded by the N-End Rule Pathway▿

Schnupf, Pamela, Zhou, Jianmin, Varshavsky, Alexander, Portnoy, Daniel A.

The intracellular pathogen Listeria monocytogenes escapes from a phagosomal compartment into the cytosol by secreting the pore-forming cytolysin listeriolysin O (LLO). During the proliferation of L....

Mice Lacking the Type I Interferon Receptor Are Resistant to Listeria monocytogenes

Auerbuch, Victoria, Brockstedt, Dirk G., Meyer-Morse, Nicole, O'Riordan, Mary, Portnoy, Daniel A.

Listeria monocytogenes is a facultative intracellular pathogen that induces a cytosolic signaling cascade resulting in expression of interferon (IFN)-β. Although type I IFNs are critical in viral...

Distinct TLR- and NLR-Mediated Transcriptional Responses to an Intracellular Pathogen

Leber, Jess H, Crimmins, Gregory T, Raghavan, Sridharan, Meyer-Morse, Nicole P, Cox, Jeffery S, Portnoy, Daniel A

How the innate immune system tailors specific responses to diverse microbial infections is not well understood. Cells use a limited number of host receptors and signaling pathways to both...

Proteolytic Pathways of Activation and Degradation of a Bacterial Phospholipase C during Intracellular Infection by Listeria monocytogenes

Marquis, Hélène, Goldfine, Howard, Portnoy, Daniel A.

Listeria monocytogenes is a facultative intracellular bacterial pathogen that spreads cell to cell without exposure to the extracellular environment. Bacterial cell-to-cell spread is mediated in part...

Pivotal role of VASP in Arp2/3 complex–mediated actin nucleation, actin branch-formation, and Listeria monocytogenes motility

Skoble, Justin, Auerbuch, Victoria, Goley, Erin D., Welch, Matthew D., Portnoy, Daniel A.

The Listeria monocytogenes ActA protein mediates actin-based motility by recruiting and stimulating the Arp2/3 complex. In vitro, the actin monomer-binding region of ActA is critical for stimulating...

The Listeria monocytogenes hemolysin has an acidic pH optimum to compartmentalize activity and prevent damage to infected host cells

Glomski, Ian J., Gedde, Margaret M., Tsang, Albert W., Swanson, Joel A., Portnoy, Daniel A.

Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from a phagosome and grows in the host cell cytosol. The pore-forming cholesterol-dependent cytolysin,...

The cell biology of Listeria monocytogenes infection: the intersection of bacterial pathogenesis and cell-mediated immunity

Portnoy, Daniel A., Auerbuch, Victoria, Glomski, Ian J.

Listeria monocytogenes has emerged as a remarkably tractable pathogen to dissect basic aspects of cell biology, intracellular pathogenesis, and innate and acquired immunity. In order to maintain its...

Three Regions within Acta Promote Arp2/3 Complex-Mediated Actin Nucleation and Listeria monocytogenes Motility

Skoble, Justin, Portnoy, Daniel A., Welch, Matthew D.

The Listeria monocytogenes ActA protein induces actin-based motility by enhancing the actin nucleating activity of the host Arp2/3 complex. Using systematic truncation analysis, we identified a...

Listeria monocytogenes multidrug resistance transporters activate a cytosolic surveillance pathway of innate immunity

Crimmins, Gregory T., Herskovits, Anat A., Rehder, Kai, Sivick, Kelsey E., Lauer, Peter, Dubensky, Thomas W., ...

To gain insight into the interaction of intracellular pathogens with host innate immune pathways, we performed an unbiased genetic screen of Listeria monocytogenes mutants that induced an enhanced or...

Suppression of Cell-Mediated Immunity following Recognition of Phagosome-Confined Bacteria

Bahjat, Keith S., Meyer-Morse, Nicole, Lemmens, Edward E., Shugart, Jessica A., Dubensky, Thomas W., Brockstedt, Dirk G., ...

Listeria monocytogenes is a facultative intracellular pathogen capable of inducing a robust cell-mediated immune response to sub-lethal infection. The capacity of L. monocytogenes to escape from the...

Killed but Metabolically Active Bacillus anthracis Vaccines Induce Broad and Protective Immunity against Anthrax▿

Skoble, Justin, Beaber, John W., Gao, Yi, Lovchik, Julie A., Sower, Laurie E., Liu, Weiqun, ...

Bacillus anthracis is the causative agent of anthrax. We have developed a novel whole-bacterial-cell anthrax vaccine utilizing B. anthracis that is killed but metabolically active (KBMA). Vaccine...