Gut Instinct: Salmonella Bacteria's Molecular Tactics to Cause Illness

By Richard Harth

Hundreds of trillions of bacteria make their home in the vertebrate gut. Though many of these microbes perform helpful duties for their host, others—the pathogens—are unwelcome visitors, causing disease.

Salmonella typhimurium is one such pathogenic bacterium. It has evolved sophisticated means of growth, replication, transport and survival within the forbidding environment of the body, where it is responsible for most cases of foodborne illness. Yixin Shi, a researcher at ArizonaStateUniversity's Biodesign Institute, has taken a keen interest in the regulatory mechanisms that allow Salmonella bacteria to overcome their surroundings and continuously modify both their own and their host's responses in order to stay alive.

By cooperating with the Dr. Roy Curtiss' lab in the Biodesign Institute, Shi's research, which appears in the Proceedings of the National Academy of Sciences, (PNAS) unveils a key survival circuit, which activates a signaling cascade, switching on or off a suite of genes necessary to circumvent the body's multiple defense mechanisms.

The bacteria are tenacious, surviving acidic pH conditions, digestive enzymes, bile salts, antimicrobial peptides, and other hazards as they pass through the stomach and intestine, and invade the mucosa of the small intestine. Once they make contact with the intestinal lumen, their goal is to secure a safe haven—within the cells of the intestinal epithelium.

To reach this sanctuary, Salmonella first invite themselves in by secreting specific protein factors derived from a region of DNA known as the SalmonellaPathogenicityIsland 1 or SPI-1. These factors trick the body, inducing the reorganization of the host cell's cytoskeleton. Epithelial cells respond to the Salmonella secretions by surrounding the bacterial cell in a membrane-bound balloon—the Salmonella Containing Vacuole (SCV). Once the bacterium is taken up in the SCV by the epithelial cell, this secretion system is no longer needed and is switched off. At the same time, another system, SPI-2 is activated and will respond to the altered environment of the internalized Salmonella.

As the Salmonella penetrates through the epithelial layer, it encounters a dense population of macrophages that normally act to engulf and digest pathogens and debris. Unlike other gut commensal microbes—E. coli for example—Salmonella is able to survive and replicate within SCV of these macrophages, which eventually transport it to organs including the liver and spleen. "The host cells isolate nutrients from bacteria," Shi explains. "They may deplete metal ions, nucleotides, and amino acids which are essential for bacterial life and growth. In this way, Salmonella are essentially starved to death."

But the Salmonella are prepared, and respond— first by sensing the new conditions, then synthesizing proteins allowing them to acquire nutrients from this new environment while switching on genes girding the bacteria against destructive host peptides.