scholarly journals Microgravity as a Novel Environmental Signal Affecting Salmonella enterica Serovar Typhimurium Virulence

2000 ◽  
Vol 68 (6) ◽  
pp. 3147-3152 ◽  
Author(s):  
Cheryl A. Nickerson ◽  
C. Mark Ott ◽  
Sarah J. Mister ◽  
Brian J. Morrow ◽  
Lisa Burns-Keliher ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Salmonella Enterica ◽  
Simulated Microgravity ◽  
Normal Gravity ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Acid Stress ◽  
Disease Process ◽  
Murine Spleen ◽  
Serovar Typhimurium ◽  
Macrophage Killing

ABSTRACT The effects of spaceflight on the infectious disease process have only been studied at the level of the host immune response and indicate a blunting of the immune mechanism in humans and animals. Accordingly, it is necessary to assess potential changes in microbial virulence associated with spaceflight which may impact the probability of in-flight infectious disease. In this study, we investigated the effect of altered gravitational vectors on Salmonella virulence in mice. Salmonella enterica serovar Typhimurium grown under modeled microgravity (MMG) were more virulent and were recovered in higher numbers from the murine spleen and liver following oral infection compared to organisms grown under normal gravity. Furthermore, MMG-grown salmonellae were more resistant to acid stress and macrophage killing and exhibited significant differences in protein synthesis than did normal-gravity-grown cells. Our results indicate that the environment created by simulated microgravity represents a novel environmental regulatory factor of Salmonellavirulence.

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

2008 ◽  
Vol 76 (10) ◽  
pp. 4445-4454 ◽  
Author(s):  
Andrea L. Zbell ◽  
Susan E. Maier ◽  
Robert J. Maier
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Acid Stress ◽  
Wild Type ◽  
Reverse Transcription Pcr ◽  
Serovar Typhimurium ◽  
Low Levels ◽  
And Function ◽  
Mutant Cells

ABSTRACT Salmonella enterica serovar Typhimurium, a common enteric pathogen, possesses three NiFe uptake-type hydrogenases. The results from mouse infection studies suggest that the H2 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.

scholarly journals Constitutive Acid Sphingomyelinase Enhances Early and Late Macrophage Killing of Salmonella enterica Serovar Typhimurium

2007 ◽  
Vol 75 (11) ◽  
pp. 5346-5352 ◽  
Author(s):  
Bruce D. McCollister ◽  
Jesse T. Myers ◽  
Jessica Jones-Carson ◽  
Dennis R. Voelker ◽  
Andrés Vázquez-Torres
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Acid Sphingomyelinase ◽  
Wild Type ◽  
Serovar Typhimurium ◽  
Important Player ◽  
Phagocyte Oxidase ◽  
Macrophage Killing

ABSTRACT We have identified acid sphingomyelinase (ASM) as an important player in the early and late anti-Salmonella activity of macrophages. A functional ASM participated in the killing activity of macrophages against wild-type Salmonella enterica serovar Typhimurium. The role of ASM in early macrophage killing of Salmonella appears to be linked to an active NADPH phagocyte oxidase enzymatic complex, since the flavoprotein inhibitor diphenyleneiodonium not only blocked a productive respiratory burst but also abrogated the survival advantage of Salmonella in macrophages lacking ASM. Lack of ASM activity also increased the intracellular survival of an isogenic ΔspiC::FRT Salmonella strain deficient in a translocator and effector of the Salmonella pathogenicity island 2 (SPI2) type III secretion system, suggesting that the antimicrobial activity associated with ASM is manifested regardless of the SPI2 status of the bacteria. Constitutively expressed ASM is responsible for the role that this lipid-metabolizing hydrolase plays in the innate host defense of macrophages against Salmonella. Accordingly, the ASM activity and intracellular concentration and composition of ceramide, gangliosides, and neutral sphingolipids did not increase upon Salmonella infection. Salmonella triggered, nonetheless, a significant increase in the secreted fraction of ASM. Collectively, these findings have elucidated a novel role for constitutive ASM in the anti-Salmonella activity of murine macrophages.

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