The role of the Shigella flexneri yihE gene in LPS synthesis and virulence.
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.
Edwards-Jones
Bryn
B
Centre for Molecular Microbiology and Infection, Department of Biological Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
Langford
Paul R
PR
Molecular Infectious Diseases Group, Department of Paediatrics, Faculty of Medicine, Imperial College London, St Mary's Campus, London W2 1PG, UK.
Kroll
J Simon
JS
Molecular Infectious Diseases Group, Department of Paediatrics, Faculty of Medicine, Imperial College London, St Mary's Campus, London W2 1PG, UK.
Yu
Jun
J
Centre for Molecular Microbiology and Infection, Department of Biological Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
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
D001426:Bacterial Proteins; D008070:Lipopolysaccharides; D005690:Galactose