The regulation of polyamines is essential for the physiological function of organisms. Simplistically, polyamines are organic cations that interact with RNA, including ribosomes and translational machinery. Both the lack of and an excess of polyamines confer lethal phenotypes, though the molecular mechanism behind this is unclear. Despite their critical role, the functions of polyamines are not well known.
James Slauch, a professor microbiology whose research interests focus on Salmonella genetics and pathogenesis, and Yumi Iwadate, a postdoctoral fellow at the University of Illinois, recently characterized the inner membrane protein PaeA (YtfL) and its role in polyamine regulation. Their findings were outlined in the article, “PaeA (YtfL) protects from cadaverine and putrescine stress in Salmonella Typhimurium and E. coli,” published in the journal Molecular Microbiology.
Professor Slauch and members of his lab had previously determined that PaeA plays a role in the virulence of Salmonella; therefore, the protein was of great interest to the research group. “Salmonella survives and replicates in macrophages, making it a particularly dangerous pathogen," Slauch said.
In the process of characterizing PaeA, Iwadate questioned if the protein could survive in a low pH environment, characteristic of the conditions in which Salmonella replicates in the macrophage. Through a series of physiological experiments, they determined that, in this environment, the cells produced the polyamine cadaverine. The paeA mutant was sensitive to the cadaverine in stationary phase.
From this, they determined that polyamines play a critical role in Salmonella physiology, and that Salmonella and the related organism E. coli synthesize and transport the polyamines cadaverine and putrescine to regulate physiological levels in response to various stresses, including low pH.
Subsequent work in the lab is focused on the relationship between polyamines and magnesium. It is known that the intracellular magnesium concentration drops when Salmonella is engulfed in the phagosome of a macrophage. Magnesium and polyamines are functionally similar - both are cations that can counteract the phosphates in RNA. Because of these similarities, Slauch believes that Salmonella induces polyamine synthesis to counteract the lowered magnesium concentration. Additionally, the bacterium activates magnesium pumps to reacquire the cation. This results in an abundance of cations, magnesium and polyamines. In order to prevent lethality, PaeA must export the excess polyamines under these conditions.
Prior to this project, the function of PaeA was uncharacterized; however, Slauch's novel findings have provided insight into the protein's transporter function. Very similar proteins are found in a wide variety of bacterial species. This characterization may also have clinical implications as PaeA is known to be involved in the virulence of Salmonella. The group is continuing its study of this protein. They also hope to explore PaeA's relationship to magnesium and biochemically prove its function as an exporter.
The National Institutes of Health supported this work.