Kramer RW~Lesser CF, 2007

Pubmed ID 17305427
Title Yeast functional genomic screens lead to identification of a role for a bacterial effector in innate immunity regulation.
Authors Roger W Kramer, Naomi L Slagowski, Ngozi A Eze, Kara S Giddings, Monica F Morrison, Keri A Siggers, Michael N Starnbach, Cammie F Lesser
Abstract Numerous bacterial pathogens manipulate host cell processes to promote infection and ultimately cause disease through the action of proteins that they directly inject into host cells. Identification of the targets and molecular mechanisms of action used by these bacterial effector proteins is critical to understanding pathogenesis. We have developed a systems biological approach using the yeast Saccharomyces cerevisiae that can expedite the identification of cellular processes targeted by bacterial effector proteins. We systematically screened the viable yeast haploid deletion strain collection for mutants hypersensitive to expression of the Shigella type III effector OspF. Statistical data mining of the results identified several cellular processes, including cell wall biogenesis, which when impaired by a deletion caused yeast to be hypersensitive to OspF expression. Microarray experiments revealed that OspF expression resulted in reversed regulation of genes regulated by the yeast cell wall integrity pathway. The yeast cell wall integrity pathway is a highly conserved mitogen-activated protein kinase (MAPK) signaling pathway, normally activated in response to cell wall perturbations. Together these results led us to hypothesize and subsequently demonstrate that OspF inhibited both yeast and mammalian MAPK signaling cascades. Furthermore, inhibition of MAPK signaling by OspF is associated with attenuation of the host innate immune response to Shigella infection in a mouse model. These studies demonstrate how yeast systems biology can facilitate functional characterization of pathogenic bacterial effector proteins.
Citation PLoS Pathog. 2007; 3:e21

Datasets

Download the list of datasets
Papers Phenotype Conditions Collection Tested mutants Data Details
Kramer RW~Lesser CF, 2007 growth (colony size) Shigella OspF expression [unknown] hap alpha ~4,773 Discrete

Curation history

Data

Nov. 10, 2014 Data to request.
Nov. 19, 2014 Data requested.
Aug. 17, 2016 Data requested.
April 25, 2017 Data abandoned.
April 25, 2017 Data to load.
April 28, 2017 Data loaded.

Tested strains

Nov. 10, 2014 Tested strains to request.
Nov. 19, 2014 Tested strains requested.
Aug. 17, 2016 Tested strains requested.
April 25, 2017 Tested strains abandoned.