Novel Mechanism in Salmonella Virulence, Drug Susceptibility

Abstract

Researchers have discovered a novel mechanism in Salmonella that affects its virulence and its susceptibility to antibiotics by changing its production of proteins in order to respond to inhospitable conditions.Although the mechanism had not been recognized before, the scientists were intrigued to find evidence of a similar mechanism conserved throughout the course of evolution. The findings were published July 30 in Molecular Cell with the senior study author being Ferric C. Fang, MD, Professor of Microbiology, Laboratory Medicine, and Medicine at the University of Washington.While screening mutant Salmonella that were resistant to S-nitrosoglutathione, a form of nitric oxide that normally stops the bacteria from dividing, the researchers found mutations in 2 uncharacterized genes, poxA (yjeA or STM4344) and yjeK (STM4333), putatively involved in tRNA and lysine biosynthesis, respectively. “In a number of phylogenetically distant bacterial species, the poxA and yjeK genes are linked to each other and to a third gene, efp, encoding the bacterial elongation factor P (EF-P) involved in protein synthesis,” Fang and co-authors note.“Here, we report that these genes operate in a common pathway critical for virulence and resistance to several classes of antibiotics,” the report states. “Two-dimensional gel analysis revealed that the poxA and yjeK mutant strains display nearly identical phenotypes and changes in protein expression profiles, including several proteins involved in metabolism and factors encoded by the Salmonella pathogenicity island, SPI-1. Furthermore we demonstrate by biochemical means that PoxA is the enzyme responsible for the previously observed posttranslational modification of EF-P.”“Our data demonstrate that YjeK, PoxA, and EF-P affect the expression of factors that play an essential role in Salmonella virulence and intrinsic resistance to diverse antimicrobial compounds.” See: Molecular Cell 2010;39:209–221. (Figure 1). Researchers have discovered a novel mechanism in Salmonella that affects its virulence and its susceptibility to antibiotics by changing its production of proteins in order to respond to inhospitable conditions. Although the mechanism had not been recognized before, the scientists were intrigued to find evidence of a similar mechanism conserved throughout the course of evolution. The findings were published July 30 in Molecular Cell with the senior study author being Ferric C. Fang, MD, Professor of Microbiology, Laboratory Medicine, and Medicine at the University of Washington. While screening mutant Salmonella that were resistant to S-nitrosoglutathione, a form of nitric oxide that normally stops the bacteria from dividing, the researchers found mutations in 2 uncharacterized genes, poxA (yjeA or STM4344) and yjeK (STM4333), putatively involved in tRNA and lysine biosynthesis, respectively. “In a number of phylogenetically distant bacterial species, the poxA and yjeK genes are linked to each other and to a third gene, efp, encoding the bacterial elongation factor P (EF-P) involved in protein synthesis,” Fang and co-authors note. “Here, we report that these genes operate in a common pathway critical for virulence and resistance to several classes of antibiotics,” the report states. “Two-dimensional gel analysis revealed that the poxA and yjeK mutant strains display nearly identical phenotypes and changes in protein expression profiles, including several proteins involved in metabolism and factors encoded by the Salmonella pathogenicity island, SPI-1. Furthermore we demonstrate by biochemical means that PoxA is the enzyme responsible for the previously observed posttranslational modification of EF-P.” “Our data demonstrate that YjeK, PoxA, and EF-P affect the expression of factors that play an essential role in Salmonella virulence and intrinsic resistance to diverse antimicrobial compounds.” See: Molecular Cell 2010;39:209–221. (Figure 1).