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

Abstract

ABSTRACT 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.