Salmonella enterica Serovar Typhimurium NiFe Uptake-Type Hydrogenases Are Differentially Expressed In Vivo

Abstract

Salmonella enterica serovar Typhimurium, a common enteric pathogen, possesses three NiFe uptake-type hydrogenases. The results from mouse infection studies suggest that the H 2 oxidation capacity provided by these hydrogenases is important for virulence. Since the three enzymes are similar in structure and function, it may be expected that they are utilized under different locations and times during an infection. A recombination-based method to examine promoter activity in vivo (RIVET) was used to determine hydrogenase gene expression in macrophages, polymorphonuclear leukocyte (PMN)-like cells, and a mouse model of salmonellosis. The hyd and hya promoters showed increased expression in both murine macrophages and human PMN-like cells compared to that in the medium-only controls. Quantitative reverse transcription-PCR results suggested that hyb is also expressed in phagocytes. A nonpolar hya mutant was compromised for survival in macrophages compared to the wild type. This may be due to lower tolerance to acid stress, since the hya mutant was much more acid sensitive than the wild type. In addition, hya mutant cells were internalized by macrophages the same as wild-type cells. Mouse studies (RIVET) indicate that hyd is highly expressed in the liver and spleen early during infection but is expressed poorly in the ileum in infected animals. Late in the infection, the hyd genes were expressed at high levels in the ileum as well as in the liver and spleen. The hya genes were expressed at low levels in all locations tested. These results suggest that the hydrogenases are used to oxidize hydrogen in different stages of an infection.

Central role of liver in anticancer and radioprotective activities of Toll-like receptor 5 agonist

“…Fas-mediated apoptosis has also been implicated in the pathogenicity of Salmonella infection in mice, which is predominantly localized in the liver (36)(37)(38). Consistent with this, treatment with CBLB502 (but not with LPS) improved survival of mice infected with a lethal dose of Salmonella typhimurium (Fig.…”

Host Hydrogen Rather than That Produced by the Pathogen Is Important for Salmonella enterica Serovar Typhimurium Virulence

“…In S. Typhimurium, a portion of the fermentatively produced H 2 can be recycled primarily via the respiratory hydrogenase termed Hya (12). The physiological connection of Hya to the acid-combating FHL was discovered by studying an S. Typhimurium hya deletion strain; its phenotype supports the idea that Hya-mediated H 2 oxidation also contributes to the acid resistance of S. Typhimurium (15).…”

“…While S. Typhimurium hyb and hya genes were expressed in vivo in infected mice (15,37) and in the bloodstream of bacteremic S. enterica serovar Typhi-infected humans (23), respectively, hyc-related genes were not described as expressed in either study. While it is possible that the FHL system might enable the bacteria to survive and grow under fermentative conditions within the host intestinal tract, this idea was not supported by the recovery numbers from fresh feces (this study).…”

Role of the Hya Hydrogenase in Recycling of Anaerobically Produced H 2 in Salmonella enterica Serovar Typhimurium

“…The role of Hya is not as well characterized. Hya may be used to recycle Hyc-produced H 2 , since the hya operon is expressed at high levels during fermentative growth, or it may play a role in acid stress resistance (6,14,20,21). The hyb genes are expressed at high levels under aerobic conditions in Salmonella serovar Typhimurium, and Hyb may couple H 2 oxidation to O 2 reduction (20).…”