Space boosts bacterial virulence

Salmonella grown in space shows altered gene expression and is deadlier in mice

By | September 25, 2007

Space flight increases Salmonella virulence in mammals, PNAS reports online this week. Salmonella typhimurium grown on a space shuttle mission showed altered gene expression and was more lethal to mice than control Salmonella grown on the ground. This work is "the first study to examine the effect of space flight on the virulence of a pathogen and the first to obtain the entire gene expression response of a bacterium to space flight," senior author Cheryl Nickerson of Arizona State University (ASU) in Tempe told The Scientist in an Email. In addition to its relevance for infectious disease risks in astronauts, the study also sheds light on bacterial behavior on Earth, especially its growth in biofilms and in the intestine, according to Max Mergeay of the Belgian Nuclear Research Center in Brussels, who was not involved in the work. Previous work on Salmonella grown in a space-flight simulator on Earth showed that these bacteria become more virulent and resistant to environmental stresses in a space-like environment. To see if these results held up in true outer space, researchers led by James Wilson of ASU sent cultures of Salmonella typhimurium aboard the Space Shuttle Atlantis in September 2006. Astronauts cultured the bacteria for one to three days. After the shuttle returned to Earth, the researchers found that mice infected with a sample of the Salmonella grown in space were more likely to die and died more quickly than mice infected with Earth-grown bacteria -- the same result that the researchers had found with space-flight simulators. The authors discovered that 167 genes were expressed differentially between the space- and ground-grown samples. They also found evidence that a regulatory protein called Hfq, which regulates messenger RNA translation in response to stress and can alter Salmonella virulence, likely plays a major role in Salmonella responses to the space-flight environment. The flight cultures showed significantly reduced levels of Hfq expression. Some research has indicated that Hfq expression should increase with increasing virulence, making the decrease in Hfq "particularly puzzling," according to Lionello Bossi of the National Center of Scientific Research in France, who was not a co-author. But other work has shown that bacterial virulence can sometimes increase when classic virulence genes are down-regulated, Nickerson said. "This suggests exciting new insight in terms of how these pathogens are causing disease in our body." It's thought that the space between microvilli protrusions on intestinal cells creates a free-fall environment much like that encountered in outer space, explained co-author Kerstin Höner zu Bentrup of Tulane University Health Sciences Center in New Orleans. "We can actually mimic now what's going on in an environment that Salmonella sees in your gut shortly before it infects the cells." According to Laura Frost of the University of Alberta in Canada, who was not involved in the study, activation of Hfq-controlled genes is good evidence that stress responses are activated in bacteria grown in space. "The interesting thing about this experiment is that low gravity appears to be a stress that the bacteria can detect." The authors also found that flight samples showed evidence of increased biofilm formation, which could help explain their increased virulence, said Höner zu Bentrup. "Biofilm formation is a major player in virulence," largely because bacteria aggregated in biofilms are less susceptible to host defense mechanisms, she told The Scientist. The space-flight results largely matched those from the ground-based simulator, Höner zu Bentrup said. "I think we were all very surprised to see how well they aligned, because the ground-based experiments can never really reflect what's going on in space," she told The Scientist. However, the simulator "cannot accurately model all aspects of space flight," Nickerson said. "There are important differences between the two environments that we always need to keep in mind." Melissa Lee Phillips Links within this article J.W. Wilson, "Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq," PNAS, published online September 24, 2007. K.R. Chi, "NIH in space?" The Scientist, July 24, 2007. N.S. Halim, "The positive side of Salmonella," The Scientist, February 21, 2000. Cheryl Nickerson G. Sonnenfeld, W.T. Shearer, "Immune function during space flight," Nutrition, October 2002. N. Johnston, "Debaffling biofilms," The Scientist, August 2, 2004. Max Mergeay C.A. Nickerson et al., "Microbial responses to microgravity and other low-shear environments," Microbiology and Molecular Biology Reviews, June 2004. N. Figueroa-Bossi et al., "Loss of Hfq activates the sigmaE-dependent envelope stress response in Salmonella enterica," Molecular Microbiology, November 2006. A. Sittka, "The RNA chaperone Hfq is essential for the virulence of Salmonella typhimurium," Molecular Microbiology, January 2007. Lionello Bossi D.S. Merrell et al., "Host-induced epidemic spread of the cholera bacterium," Nature, June 6, 2002. P. Guo et al., "A hydrodynamic mechanosensory hypothesis for brush border microvilli," American Journal of Physiology Renal Physiology, October 2000. Kerstin Höner zu Bentrup Laura Frost C.A. Fux et al., "Survival strategies of infectious biofilms," Trends in Microbiology, January 2005.


October 2, 2007

The fact that nearly identical results were obtained both in space as well as in the ground-based simulator would lead to the conclusion that growth in space had nothing at all to do with the increased virulence of the Salmonella. Rather there seems to be something inherent in the actuall experiental design that caused such an affect, and that loss of gravity does not appear to be the cause of the virulence change, either directly or indirectly. If the change in virulence were in fact due to loss of gravity, one would have expected to not see the same result on the ground.

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