The periplasmic chaperone Skp is required for successful Salmonella Typhimurium infection in a murine typhoid model

Rowley, G., Skovierova, H., Stevenson, A., Rezuchova, B., Homerova, D., Lewis, C., Sherry, A., Kormanec, J. and Roberts, M. (2011) The periplasmic chaperone Skp is required for successful Salmonella Typhimurium infection in a murine typhoid model. Microbiology, 157(3), pp. 848-858. (doi: 10.1099/mic.0.046011-0) (PMID:21148205)

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Publisher's URL: http://dx.doi.org/10.1099/mic.0.046011-0

Abstract

The alternative sigma factor (YE (rpoE) is essential for survival in vivo of Salmonella Typhimurium but is dispensable during growth in the laboratory. We have been identifying sigma(E)-regulated genes and studying their regulation and function to elucidate their potential role in the severe attenuation of S. Typhimurium rpoE mutants. In this study we identify five promoters that control the rseP, yaeT (bamA), skp region. A confirmed sigma(E)-dependent promoter, yaeTp1, and a second downstream promoter, yaeTp2, are located within the upstream gene rseP and direct expression of the downstream genes. The only known function of RseP is sigma(E) activation, and it is therefore not expected to be essential for S. Typhimurium in vitro. However, it proved impossible to delete the entire rseP gene due to the presence of internal promoters that regulate the essential gene yae T. We could inactivate rseP by deleting the first third of the gene, leaving the yaeT promoters intact. Like the rpoE mutant, the rseP mutant exhibited severe attenuation in vivo. We were able to delete the entire coding sequence of skp, which encodes a periplasmic chaperone involved in targeting misfolded outer-membrane proteins to the beta-barrel assembly machinery. The skp mutant was attenuated in mice after oral and parenteral infection. Virulence could be complemented by providing skp in trans but only by linking it to a heterologous sigma(E)-regulated promoter. The reason the skp mutant is attenuated is currently enigmatic, but we know it is not through increased sensitivity to a variety of RpoE-activating host stresses, such as H2O2, polymyxin B and high temperature, or through altered secretion of effector proteins by either the Salmonella pathogenicity island (SPI)-1 or the SPI-2 type Ill secretion system

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Roberts, Professor Mark and Stevenson, Mr Andrew and Linn, Dr Aileen
Authors: Rowley, G., Skovierova, H., Stevenson, A., Rezuchova, B., Homerova, D., Lewis, C., Sherry, A., Kormanec, J., and Roberts, M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Microbiology
ISSN:1350-0872

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
378891Secretomes of bacterial foodborne pathogens and functional assessment during interaction with intestinal epitheliumDavid SmithBiotechnology and Biological Sciences Research Council (BBSRC)BB/C508485/1Infection Immunity and Inflammation Life Sciences