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Your search keyword '"Ellen S. Everson"' showing total 2 results
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2 results on '"Ellen S. Everson"'

1. Modulation of Antigenic Location Converts Chronic into Acute Infection by Forcing CD8+ T Cell Recognition

Author

Fanny Tzelepis, Valeria Alcon, Renu Dudani, Komal Gurnani, Ahmed Zafer, Ellen S. Everson, Kevin G. Young, Holger Rüssmann, Lakshmi Krishnan, and Subash Sad

Subjects
Biology (General), QH301-705.5
Abstract

Pathogens that reside in the phagosomes of infected cells persist despite the presence of potent T cell responses. We addressed the mechanism of immune evasion by using a mouse model of Salmonella typhimurium (ST). Recombinants of ST were generated that translocated antigen to the cytosol or phagosomes of infected cells. We find that the kinetics of antigen presentation and CD8+ T cell priming is accelerated by cytosolic antigen delivery, although the magnitude of CD8+ T cell response is not influenced by antigenic location. More importantly, only those targets that readily display antigen on the cell surface, owing to antigenic translocation to the cytosol, are recognized and killed by CD8+ T cells. Thus, vaccination approaches developed to control phagosomal pathogens should incorporate methods for modulating antigen presentation such that infected target cells can be readily recognized by CD8+ T cells.

Published
2012
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2. Identification of the docking site between a type III secretion system ATPase and a chaperone for effector cargo

Author

Kun Zhang, Murray S. Junop, Seiji Sugiman-Marangos, Sarah E. Allison, Brian K. Coombes, Ellen S. Everson, and Brian R. Tuinema

Subjects
ATPase, Mutant, Biochemistry, Microbiology, Mice, Animals, Secretion, Binding site, Molecular Biology, Adenosine Triphosphatases, Binding Sites, biology, Virulence, Effector, Cell Biology, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, Cell biology, Mice, Inbred C57BL, Molecular Docking Simulation, Docking (molecular), Chaperone (protein), biology.protein, Chaperone binding, bacteria, Female, Crystallization, Molecular Chaperones
Abstract

A number of Gram-negative pathogens utilize type III secretion systems (T3SSs) to inject bacterial effector proteins into the host. An important component of T3SSs is a conserved ATPase that captures chaperone-effector complexes and energizes their dissociation to facilitate effector translocation. To date, there has been limited work characterizing the chaperone-T3SS ATPase interaction despite it being a fundamental aspect of T3SS function. In this study, we present the 2.1 A resolution crystal structure of the Salmonella enterica SPI-2-encoded ATPase, SsaN. Our structure revealed a local and functionally important novel feature in helix 10 that we used to define the interaction domain relevant to chaperone binding. We modeled the interaction between the multicargo chaperone, SrcA, and SsaN and validated this model using mutagenesis to identify the residues on both the chaperone and ATPase that mediate the interaction. Finally, we quantified the benefit of this molecular interaction on bacterial fitness in vivo using chromosomal exchange of wild-type ssaN with mutants that retain ATPase activity but no longer capture the chaperone. Our findings provide insight into chaperone recognition by T3SS ATPases and demonstrate the importance of the chaperone-T3SS ATPase interaction for the pathogenesis of Salmonella.

Published
2014

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