Metabolomics Reveals Phospholipids as Important Nutrient Sources during Salmonella Growth in Bile In Vitro and In Vivo

Abstract

During the colonization of hosts, bacterial pathogens are presented with many challenges that must be overcome for colonization to occur successfully. This requires the bacterial sensing of the surroundings and adaptation to the conditions encountered. One of the major impediments to the pathogen colonization of the mammalian gastrointestinal tract is the antibacterial action of bile. Salmonella enterica serovar Typhimurium has specific mechanisms involved in resistance to bile. Additionally, Salmonella can successfully multiply in bile, using it as a source of nutrients. This accomplishment is highly relevant to pathogenesis, as Salmonella colonizes the gallbladder of hosts, where it can be carried asymptomatically and promote further host spread and transmission. To gain insights into the mechanisms used by Salmonella to grow in bile, we studied the changes elicited by Salmonella in the chemical composition of bile during growth in vitro and in vivo through a metabolomics approach. Our data suggest that phospholipids are an important source of carbon and energy for Salmonella during growth in the laboratory as well as during gallbladder infections of mice. Further studies in this area will generate a better understanding of how Salmonella exploits this generally hostile environment for its own benefit.

Repression of Salmonella entericaphoPExpression by Small Molecules from Physiological Bile

“…We have previously shown that physiological murine bile supports Salmonella growth at rates comparable to those seen in rich laboratory media (1). In order to begin characterizing the interactions between Salmonella and bile from other organisms, we obtained fresh, physiological bovine bile, adjusted its pH to match that of LB broth (around 7.3), and used it to perform Salmonella growth assays.…”

“…We have previously shown that Salmonella can successfully multiply in murine bile, despite the well-known antimicrobial properties of this physiological fluid (1,19). In order to determine the impact of bile on Salmonella gene expression, we performed transcriptome comparisons between Salmonella grown in LB broth and Salmonella grown in physiological murine bile using DNA microarrays.…”

“…Therefore, these may represent new molecules, and significant further studies will be required to determine their identities. Nevertheless, the experiments described above allowed us to identify a subset of small molecules, out of the several hundred present in bile (1), that are likely responsible for the biological activity observed.…”

“…Salmonella can invade and infect the epithelial cells lining the lumen of the gallbladder in a murine host (19). Additionally, Salmonella can successfully colonize bile, where it can grow at rates comparable to those achieved in rich culture medium in the laboratory, presumably using phospholipids as carbon and energy sources (1,19). Therefore, in order to further characterize the interactions between Salmonella and the host gallbladder environment, we used DNA microarrays to perform a transcriptome analysis of Salmonella growth in bile.…”

The Deubiquitinase Activity of the Salmonella Pathogenicity Island 2 Effector, SseL, Prevents Accumulation of Cellular Lipid Droplets

“…We have recently published a metabolomic analysis of the Salmonella infection of the intestinal tract and liver and have shown that Salmonella infection disrupts lipid metabolism in all tissues tested (3). Although the exact compounds affected vary depending on the infected tissue, it is clear that the modulation of host lipid metabolism is a common theme during infection with this pathogen.…”