ArticlePLoS pathogens2007
Yeast functional genomic screens lead to identification of a role for a bacterial effector in innate immunity regulation.
Article in PLoS pathogens, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 99 citations in OpenAlex.
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- Identification of Parthenogenesis-Inducing Effector Proteins in Wolbachia.Genome biology and evolution · 2024Article
- Mitogen-Activated Protein Kinases (MAPKs) and Enteric Bacterial Pathogens: A Complex Interplay.International journal of molecular sciences · 2023Review
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- The bacterial metalloprotease NleD selectively cleaves mitogen-activated protein kinases that have high flexibility in their activation loop.The Journal of biological chemistry · 2020Article
- Revealing eukaryotic histone-modifying mechanisms through bacterial infection.Seminars in immunopathology · 2020Review
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- Phosphothreonine Lyase Promotes p65 Degradation in a Mitogen-Activated Protein Kinase/Mitogen- and Stress-Activated Protein Kinase 1-Dependent Manner.Infection and immunity · 2019Article
- The Antibacterial and Anti-Eukaryotic Type VI Secretion System MIX-Effector Repertoire inMarine drugs · 2018Article
- A multi-phenotypic imaging screen to identify bacterial effectors by exogenous expression in a HeLa cell line.Scientific data · 2018Article
- Evolutionary Genetics of Cytoplasmic Incompatibility Genes cifA and cifB in Prophage WO of Wolbachia.Genome biology and evolution · 2018Article
- OrfX, a Nucleomodulin Required formBio · 2017Article
- Large-Scale Identification of Wolbachia pipientis Effectors.Genome biology and evolution · 2017Article
- Combinatorial actions of bacterial effectors revealed by exploiting genetic tools in yeast.Molecular systems biology · 2017Article
- VopE, aFrontiers in cellular and infection microbiology · 2017Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
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.
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