Yeast functional genomic screens lead to identification of a role for a bacterial effector in innate immunity regulation.
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 critic...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2007-02-01
|
| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC1797620?pdf=render |
| _version_ | 1818132415746408448 |
|---|---|
| author | Roger W Kramer Naomi L Slagowski Ngozi A Eze Kara S Giddings Monica F Morrison Keri A Siggers Michael N Starnbach Cammie F Lesser |
| author_facet | Roger W Kramer Naomi L Slagowski Ngozi A Eze Kara S Giddings Monica F Morrison Keri A Siggers Michael N Starnbach Cammie F Lesser |
| author_sort | Roger W Kramer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T08:36:28Z |
| format | Article |
| id | doaj.art-6161d082b9b940b2aa8b4f83a6c05b6b |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-11T08:36:28Z |
| publishDate | 2007-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-6161d082b9b940b2aa8b4f83a6c05b6b2022-12-22T01:14:20ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742007-02-0132e2110.1371/journal.ppat.0030021Yeast functional genomic screens lead to identification of a role for a bacterial effector in innate immunity regulation.Roger W KramerNaomi L SlagowskiNgozi A EzeKara S GiddingsMonica F MorrisonKeri A SiggersMichael N StarnbachCammie F LesserNumerous 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.http://europepmc.org/articles/PMC1797620?pdf=render |
| spellingShingle | Roger W Kramer Naomi L Slagowski Ngozi A Eze Kara S Giddings Monica F Morrison Keri A Siggers Michael N Starnbach Cammie F Lesser Yeast functional genomic screens lead to identification of a role for a bacterial effector in innate immunity regulation. PLoS Pathogens |
| title | Yeast functional genomic screens lead to identification of a role for a bacterial effector in innate immunity regulation. |
| title_full | Yeast functional genomic screens lead to identification of a role for a bacterial effector in innate immunity regulation. |
| title_fullStr | Yeast functional genomic screens lead to identification of a role for a bacterial effector in innate immunity regulation. |
| title_full_unstemmed | Yeast functional genomic screens lead to identification of a role for a bacterial effector in innate immunity regulation. |
| title_short | Yeast functional genomic screens lead to identification of a role for a bacterial effector in innate immunity regulation. |
| title_sort | yeast functional genomic screens lead to identification of a role for a bacterial effector in innate immunity regulation |
| url | http://europepmc.org/articles/PMC1797620?pdf=render |
| work_keys_str_mv | AT rogerwkramer yeastfunctionalgenomicscreensleadtoidentificationofaroleforabacterialeffectorininnateimmunityregulation AT naomilslagowski yeastfunctionalgenomicscreensleadtoidentificationofaroleforabacterialeffectorininnateimmunityregulation AT ngoziaeze yeastfunctionalgenomicscreensleadtoidentificationofaroleforabacterialeffectorininnateimmunityregulation AT karasgiddings yeastfunctionalgenomicscreensleadtoidentificationofaroleforabacterialeffectorininnateimmunityregulation AT monicafmorrison yeastfunctionalgenomicscreensleadtoidentificationofaroleforabacterialeffectorininnateimmunityregulation AT keriasiggers yeastfunctionalgenomicscreensleadtoidentificationofaroleforabacterialeffectorininnateimmunityregulation AT michaelnstarnbach yeastfunctionalgenomicscreensleadtoidentificationofaroleforabacterialeffectorininnateimmunityregulation AT cammieflesser yeastfunctionalgenomicscreensleadtoidentificationofaroleforabacterialeffectorininnateimmunityregulation |