title: The role of the Shigella flexneri yihE gene in LPS synthesis and virulence.
abstract: Previously, the authors have shown that inactivation of Shigella flexneri yihE, a gene of unknown function upstream of dsbA, which encodes a periplasmic disulphide catalyst, results in a global change of gene expression. Among the severely down-regulated genes are galETKM, suggesting that the yihE mutant, Sh54, may inefficiently produce the UDP-glucose and UDP-galactose required for LPS synthesis. This paper demonstrates that LPS synthesis in Sh54 is impaired. As a result, Sh54 is unable to polymerize host cell actin, due to aberrant localization of IcsA, or to cause keratoconjunctivitis in guinea pigs. Furthermore, Sh54 is more sensitive to some antimicrobial agents, and exhibits epithelial cytotoxicity characteristic of neither wild-type nor dsbA mutants. Supplying galETK in trans restores LPS synthesis and corrects all the defects. Hence, it is clear that the Shigella yihE gene is important not only in regulating global gene expression, as shown previously, but also in virulence through LPS synthesis via regulating the expression of the galETK operon.
authors.affiliation: Centre for Molecular Microbiology and Infection, Department of Biological Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Bryn
authors.initials: B
authors.lastname: Edwards-Jones
authors.affiliation: Molecular Infectious Diseases Group, Department of Paediatrics, Faculty of Medicine, Imperial College London, St Mary's Campus, London W2 1PG, UK.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Langford
authors.affiliation: Molecular Infectious Diseases Group, Department of Paediatrics, Faculty of Medicine, Imperial College London, St Mary's Campus, London W2 1PG, UK.
authors.forename: J Simon
authors.initials: JS
authors.lastname: Kroll
authors.affiliation: Centre for Molecular Microbiology and Infection, Department of Biological Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D004405:Dysentery, Bacillary / Q000382:microbiology; D005690:Galactose / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006168:Guinea Pigs; D006367:HeLa Cells; D006801:Humans; D007637:Keratoconjunctivitis / Q000382:microbiology / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000378:metabolism*; D009154:Mutation; D012763:Shigella flexneri / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D008070:Lipopolysaccharides; D005690:Galactose