HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplementary tables All Versions of this Article: mic.0.030429-0v1 155/9/2919    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Google Scholar Articles by Wright, J. A. Articles by Bryant, C. E. PubMed PubMed Citation Articles by Wright, J. A. Articles by Bryant, C. E. Agricola Articles by Wright, J. A. Articles by Bryant, C. E.

Multiple redundant stress resistance mechanisms are induced in Salmonella enterica serovar Typhimurium in response to alteration of the intracellular environment via TLR4 signalling

John A. Wright^1,,

Sabine S. Tötemeyer^1,,

¹ Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK
² Molecular Microbiology Group, Institute of Food Research, Norwich NR4 7UA, UK
³ School of Clinical Veterinary Sciences, University of Bristol, Langford House, Langford, Bristol BS40 5DU, UK

Toll-like receptor 4 (TLR4) senses bacterial LPS and is required for the control of systemic Salmonella enterica serovar Typhimurium infection in mice. The mechanisms of TLR4 activation and its downstream signalling cascades are well described, yet the direct effects on the pathogen of signalling via this receptor remain unknown. To investigate this we used microarray-based transcriptome profiling of intracellular S. Typhimurium during infection of primary bone marrow-derived macrophages from wild-type and TLR4-deficient mice. We identified 17 S. Typhimurium genes that were upregulated in the presence of functional TLR4. Nine of these genes have putative functions in oxidative stress resistance. We therefore examined S. Typhimurium gene expression during infection of NADPH oxidase-deficient macrophages, which lack normal oxidative killing mechanisms. We identified significant overlap between the ‘TLR4-responsive’ and ‘NADPH oxidase-responsive’ genes. This is new evidence for a link between TLR4 signalling and NADPH oxidase activity. Interestingly, with the exception of a dps mutant, S. Typhimurium strains lacking individual TLR4- and/or oxidative stress-responsive genes were not attenuated during intravenous murine infections. Our study shows that TLR4 activity, either directly or indirectly, induces the expression of multiple stress resistance genes during the intracellular life of S. Typhimurium.

Correspondence
Clare E. Bryant
ceb27{at}cam.ac.uk

These authors contributed equally to this work.

Present address: Division of Microbial Diseases, UCL Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD, UK.

Present address: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK.

||Present address: School of Genetics and Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland.

The ArrayExpress accession numbers for the complete gp91^–/–, TLR4^–/– and hydrogen peroxide datasets associated with this paper are E-MEXP-1089 and E-MEXP-1067.

Five supplementary tables are available with the online version of this paper.