Fis Is Essential for Yersinia pseudotuberculosis Virulence and Protects against Reactive Oxygen Species Produced by Phagocytic Cells during Infection.

All three pathogenic Yersinia species share a conserved virulence plasmid that encodes a Type 3 Secretion System (T3SS) and its associated effector proteins. During mammalian infection, these effectors are injected into innate immune cells, where they block many bactericidal functions, including the production of reactive oxygen species (ROS). However, Y.

CD8(+) T cells specific to a single Yersinia pseudotuberculosis epitope restrict bacterial replication in the liver but fail to provide sterilizing immunity.

CD8(+) T cells use contact-dependent cytolysis of target cells to protect the host against intracellular pathogens. We have previously shown that CD8(+) T cells and perforin are required to protect against the extracellular pathogen Yersinia pseudotuberculosis. Here we establish an experimental system where CD8(+) T cells specific to a single model antigen are the only memory response present at time of challenge.

Identification of MrtAB, an ABC transporter specifically required for Yersinia pseudotuberculosis to colonize the mesenteric lymph nodes.

A highly conserved virulence plasmid encoding a type III secretion system is shared by the three Yersinia species most pathogenic for mammals. Although factors encoded on this plasmid enhance the ability of Yersinia to thrive in their mammalian hosts, the loss of this virulence plasmid does not eliminate growth or survival in host organs. Most notably, yields of viable plasmid-deficient Yersinia pseudotuberculosis (Yptb) are indistinguishable from wild-type Yptb within mesenteric lymph nodes.

Analyzing microbial disease at high resolution: following the fate of the bacterium during infection.

The study of bacterial pathogens has historically been viewed with a wide lens, providing a picture of how bacterial populations act as groups, but with insufficient resolution to see how microorganisms act as individuals. For most bacterial pathogens, we do not know the minimal number of microbes that initiate infection in a particular organ site, the number that spread outside the site of initial colonization, and how many persist over time. Recent studies have begun to shed light on these points, and the development of new techniques has dramatically increased the ability of researchers to interrogate these problems.

Listeria monocytogenes 6-Phosphogluconolactonase mutants induce increased activation of a host cytosolic surveillance pathway.

Infection with wild-type Listeria monocytogenes activates a host cytosolic surveillance response characterized by the expression of beta interferon (IFN-beta). We performed a genetic screen to identify L. monocytogenes transposon insertion mutants that induced altered levels of host IFN-beta expression.

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

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 diminished host innate immune response. Here, we show that the major facilitator superfamily of bacterial multidrug resistance transporters (MDRs) controlled the magnitude of a host cytosolic surveillance pathway, leading to the production of several cytokines, including type I IFN. Mutations mapping to repressors of MDRs resulted in ectopic expression of their cognate transporters, leading to host responses that were increased up to 20-fold over wild-type bacteria, and a 20-fold decrease in bacterial growth in vivo.

Distinct TLR- and NLR-mediated transcriptional responses to an intracellular pathogen.

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 discriminate among extracellular and intracellular microbes, and also to generate responses commensurate to each threat. Here, we have addressed these questions by using DNA microarrays to monitor the macrophage transcriptional response to the intracellular bacterial pathogen Listeria monocytogenes.

Early regeneration genes: Building a molecular profile for shared expression in cornea-lens transdifferentiation and hindlimb regeneration in Xenopus laevis.

Recent studies in Xenopus laevis have begun to compare gene expression during regeneration with that of the original development of specific structures (e.g., the hindlimb and lens), while other studies have sought differences in gene expression between regeneration-competent and regeneration-incompetent stages.