Scientists may have at last unraveled the Typhoid Mary mystery, more than 100 years after Mary Mallon infected scores of people in New York. According to the new study, salmonella has the ability to hang back during the first wave of attack from immune cells, later modifying these very cells to become more suitable for the bacteria’s needs and growth.
The research by Denise Monack, from the Stanford University School of Medicine, could explain how Mary Mallon, better known as Typhoid Mary, could carry the disease but showed no signs of infection herself. Mary was an Irish immigrant who worked as a cook for several prominent New York families and was discovered to be the source of the typhoid outbreak by George Soper, a sanitation worker, in 1903, reports the Los Angeles Times.
Mary was linked to the typhoid cases in New York and was quarantined from 1907 until 1910. She would change her name and resume working in various homes as a cook when another typhoid infection broke out in 1915. Mary was arrested and quarantined to North Brother Island in the East River until her death in 1938. She was a healthy carrier of the disease but it was unclear how she was able to spread it without showing any symptoms, such as diarrhea or rashes, of typhoid fever. Typhoid Mary was linked to as many as 50 deaths.
The disease can prevented through vaccination and can be treated with antibiotics, but it still infects millions of people annually. The LA Times reports typhoid fever caused 16 million illnesses and 600,000 deaths worldwide, while a more recent study indicates a higher number of illnesses, 21 million, with fewer deaths, estimated between 200,000 and 600,000.
Monack’s research discovered that the strain of salmonella, Salmonella typhi (S. typhi), responsible for typhoid fever can hide during the initial wave of defense, by the immune cells known as macrophages. “Inflammatory substances secreted by other immune cells stir macrophages into an antimicrobial frenzy. If you’re not a good pathogen, you’ll be wiped out after several days of causing symptoms,” said Monack in a statement.
The bacteria hides inside less-aggressive macrophages associated with anti-inflammation, such as wound healing, that occur afterward the initial wave. The bacteria can then modify the macrophages into becoming more suitable for its growth, creating healthy carriers similar to Typhoid Mary. Monack discovered this ability through experiments using Salmonella typhimurium, which causes typhoid fever in mice and is similar to the strain of bacteria in humans.
In mice, the bacteria triggered peroxide-proliferation-induced receptors (PPARs), which help regulate glucose production in macrophages, and boost glucose in the anti-inflammatory macrophages. This allowed the bacteria to multiply inside a human. “We suspect it’s releasing some as-yet-unknown PPAR-delta-stimulating virulence factor into the macrophages it infects,” said Monack. The next step is to determine how the bacteria spur PPAR-delta activity and if there is a similar mechanism found in S. typhi. Isolating this mechanism could lead to new treatments and preventative measures. Monack's study was published in the journal Cell Host & Microbe.