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Infection and Immunity, July 2009, p. 3117-3126, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00093-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Glucose and Glycolysis Are Required for the Successful Infection of Macrophages and Mice by Salmonella enterica Serovar Typhimurium{triangledown}

Steven D. Bowden,1 Gary Rowley,2 Jay C. D. Hinton,1,3 and Arthur Thompson1*

Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, United Kingdom,1 School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, United Kingdom,2 School of Genetics and Microbiology, Trinity College, Dublin 2, Ireland3

Received 23 January 2009/ Returned for modification 2 March 2009/ Accepted 13 April 2009

Salmonella is a widespread zoonotic enteropathogen that causes gastroenteritis and fatal typhoidal disease in mammals. During systemic infection of mice, Salmonella enterica serovar Typhimurium resides and replicates in macrophages within the "Salmonella-containing vacuole" (SCV). It is surprising that the substrates and metabolic pathways necessary for growth of S. Typhimurium within the SCV of macrophages have not been identified yet. To determine whether S. Typhimurium utilized sugars within the SCV, we constructed a series of S. Typhimurium mutants that lacked genes involved in sugar transport and catabolism and tested them for replication in mice and macrophages. These mutants included a mutant with a mutation in the pfkAB-encoded phosphofructokinase, which catalyzes a key committing step in glycolysis. We discovered that a pfkAB mutant is severely attenuated for replication and survival within RAW 264.7 macrophages. We also show that disruption of the phosphoenolpyruvate:carbohydrate phosphotransferase system by deletion of the ptsHI and crr genes reduces S. Typhimurium replication within RAW 264.7 macrophages. We discovered that mutants unable to catabolize glucose due to deletion of ptsHI, crr, and glk or deletion of ptsG, manXYZ, and glk showed reduced replication within RAW 264.7 macrophages. This study proves that S. Typhimurium requires glycolysis for infection of mice and macrophages and that transport of glucose is required for replication within macrophages.

* Corresponding author. Mailing address: Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, United Kingdom. Phone: (44) 1603 255181. Fax: (44) 1603 255288. E-mail: arthur.thompson{at}bbsrc.ac.uk

{triangledown} Published ahead of print on 20 April 2009.

Editor: S. R. Blanke

Infection and Immunity, July 2009, p. 3117-3126, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00093-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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