When Typhoid Mary died in 1938, in medical exile on a tiny New York island, she took untold numbers of Salmonella typhi to her grave. No one knew how the bacteria managed to thrive and not kill her. A team of microbiologists from Stanford University and the University of California, San Francisco, has found a tantalizing clue: a bacterium strain similar to the one responsible for “healthy” carriers such as Typhoid Mary shows an ability to hack the metabolism of the cells sent out to defend from infection and heal trauma.
“Salmonella is adapted to infect mammalian hosts; in fact, salmonella typhi only infects humans,” said Stanford microbiologist Denise Monack, lead author of the study published online Wednesday in the journal Cell Host and Microbe. “So it’s very interesting for me to try to understand why that is.”
The trickery, revealed in experiments with mice, involves a receptor protein that affects how macrophages – the body’s Pac-Man gobblers of foreign pathogens – get the energy required to survive. The team found that the bacteria tend to hang out with a mellower macrophage associated with the later stages of infection. Enough of the bacteria survive the more aggressive wave of attackers during the inflammatory phase of the immune response to settle in with the more placid anti-inflammatory cells, according to the study. Once inside, the bacteria essentially hack the genetic programming that sets off production of glucose for the host cell, and its own survival.
Mice infected with the salmonella strain typhimurium, known to cause symptoms of typhoid fever in rodents, showed increased activity of a protein known as peroxisome proliferator-activated receptors, or PPAR-gamma, the study found. The protein “controls the metabolic pathways in the macrophage and it allows the macrophage to bring in fatty acids to utilize them as a carbon source, for energy,” Monack said. Via Typhoid Mary case may be cracked, a century later.