Salmonella Research Today is a free monthly online journal that collates and summarizes the latest research about Salmonella, including details on salmonella typhimurium, food poisoning, infection, treatment.

Reactive oxygen species are the major antibacterials against Salmonella Typhimurium purine auxotrophs in the phagosome of RAW 264.7 cells.

Mantena RK, Wijburg OL, Vindurampulle C, Bennett-Wood VR, Walduck A, Drummond GR, Davies JK, Robins-Browne RM, Strugnell RA

Department of Microbiology and Immunology, The University of Melbourne, Vic. 3010, Australia.

Intramacrophage survival appears to be a pathogenic trait common to Salmonellae and definition of the metabolic requirements of Salmonella within macrophages might provide opportunities for novel therapeutic interventions. We show that loss of PurG function in Salmonella enterica serovar Typhimurium SL1344 leads to death of the bacterium in RAW264.7 cells, which was due to unavailability of purine nucleotides but not thiamine in the phagosome of RAW264.7 cells. Phagosomal escape of purG mutant restored growth, suggesting that the phagosomal environment, but not the cytosol, is toxic to Salmonella purine auxotrophs. NADPH oxidase inhibition restored the growth of purG mutant in RAW264.7 cells, implying that the Salmonella-containing vacuole acquires reactive oxygen species (ROS) that are lethal to purine auxotrophs. Under purine limiting conditions, purG mutant was unable to repair the damage caused by hydrogen peroxide or UV irradiation, suggesting that ROS-mediated DNA damage may have been responsible for the attenuated phenotype of purG mutant in RAW264.7 cells and in mice. These studies highlight the possibility of utilizing the Salmonella purine nucleotide biosynthetic pathway as a prospective therapeutic target and also underline the importance of metabolic pathways in assembling a comprehensive understanding of the host-pathogen interactions inside phagocytic cells.

Published 15 April 2008 in Cell Microbiol, 10(5): 1058-73.
Full-text of this article is available online (may require subscription).

© 2004-2008 Salmonella Research Today. All Rights Reserved.