title: A yeast-based genetic screen for identification of pathogenic Salmonella proteins.
abstract: Salmonella uses type III secretion systems (TTSS) to deliver pathogenic proteins into the host cells. These translocated effectors induce bacterial internalization and intracellular proliferation by targeting important cellular processes that are conserved among eukaryotes. Here, we assessed the feasibility of performing a genetic screen in yeast to identify novel Salmonella effectors, by searching for genes that produce toxicity when expressed in this model system. We identified several known TTSS-translocated effectors and found that two of them, SteC and SseF, from Salmonella enterica serovar Typhimurium, interfere with cytoskeletal dynamics as they do in mammalian cells. We also identified 11 genes of unknown function (seven from S. Typhi and four from S. Typhimurium) that display features commonly showed by effector proteins, such as a (G+C) content lower than the average for the chromosome, suggesting their acquisition by horizontal transfer processes. Five of these proteins are highly conserved only among Salmonella serovars, whereas the other six are also conserved in other pathogenic or opportunistic enterobacteria. Moreover, we identified other proteins that share specific activity domains with either translocated or bacterial-confined proteins known to be involved in pathogenesis, which might also act as virulence proteins.
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Ainel
authors.initials: A
authors.lastname: Alemán
authors.forename: Pablo
authors.initials: P
authors.lastname: Fernández-Piñar
authors.forename: Daniel
authors.initials: D
authors.lastname: Pérez-Núñez
authors.forename: Rafael
authors.initials: R
authors.lastname: Rotger
authors.forename: Humberto
authors.initials: H
authors.lastname: Martín
authors.forename: María
authors.initials: M
authors.lastname: Molina
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000633:toxicity*; D003599:Cytoskeleton / Q000187:drug effects; D015870:Gene Expression; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics; D012485:Salmonella typhi / Q000235:genetics; D012486:Salmonella typhimurium / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity*; D014170:Transformation, Genetic; D037521:Virulence Factors / Q000235:genetics / Q000633:toxicity*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors