Yeast functional genomic screens lead to identification of a role for a bacterial effector in innate immunity regulation.

摘要: Numerous bacterial pathogens manipulate host cell processes to promote infection and ultimately cause disease through the action of proteins that they directly inject into cells. Identification targets molecular mechanisms used by these effector is critical understanding pathogenesis. We have developed a systems biological approach using yeast Saccharomyces cerevisiae can expedite identification cellular targeted proteins. systematically screened viable haploid deletion strain collection for mutants hypersensitive expression Shigella type III OspF. Statistical data mining results identified several processes, including wall biogenesis, which when impaired caused be OspF expression. Microarray experiments revealed resulted in reversed regulation genes regulated integrity pathway. The pathway highly conserved mitogen-activated protein kinase (MAPK) signaling pathway, normally activated response perturbations. Together led us hypothesize subsequently demonstrate inhibited both mammalian MAPK cascades. Furthermore, inhibition associated with attenuation innate immune mouse model. These studies how biology facilitate functional characterization pathogenic