A Sick Kids researcher is developing a revealing new window on the workings of human cells–by studying how bacteria manipulate them.
Dr. John Brumell of Toronto’s Hospital for Sick Children recently shed new light on the remarkable ability of Salmonella bacteria to control human cells. And his discoveries may help answer some longstanding questions about how cells work.
Unlike most bacteria, which feed and reproduce outside our cells, Salmonella actually burrows into human cells in order to multiply.
And once inside, they seize control of the cell’s chemical machinery, switching processes on and off as they please, and subtly altering others. These manipulations turn the cell into a cozy environment for them to reproduce.
Salmonella’s manipulative abilities have biologists excited–especially since the bacteria achieve these changes by introducing just a few of their own chemicals into the cell.
Understanding how this small array of chemicals alters cell behavior so dramatically could bring scientists much closer to understanding how the cell’s machinery works in general.
For example, “How do cells sense their environment?” Brumell asked. “How do they relay those signals into the cell and tell the cell to change its activities? These are all basic questions in biology.”
Over the past year, Brumell has advanced our understanding of how Salmonella interferes with a cell’s chemical signaling system. Among other things, this system directs and controls the delivery of chemicals to various parts of the cell.
“It’s kind of like the circuitry of the cell,” Brumell said. “It’s really the control system and the bacteria have amazing ways to alter that control system.”
The signaling system directs a cell’s fleet of chemical-carrying pouches called endosomes. The endosomes shuttle back and forth, picking up chemicals manufactured near the nucleus, delivering them and returning for more. They move along a network of “microtubules” that crisscrosses the cell, directed by the system of chemical traffic signals.
The network and its associated signals have proved to be the key to one of Salmonella’s ingenious tricks. When Salmonella bacteria invade a cell, they somehow persuade it to build a protective envelope around them as they multiply. This past summer, Brumell announced his discovery that Salmonella achieves this feat by simply redirecting traffic along the cell’s control network.
A chemical produced by Salmonella orders endosomes not to complete their normal delivery routes. Instead, they are directed to bunch together around the bacteria, forming a wall around them.
Brumell is excited at the implications for basic cell biology.
Biologists studying the human cell would dearly like to understand the workings of the traffic control system that Salmonella manipulates with such ease. And Salmonella can do much more besides redirecting traffic within the cell. It can also force cells to reach out and pull them in, and can even make human cells commit suicide.
Understanding how Salmonella makes cells do these things will contribute to our understanding of “how cells do what they do,” Brumell said.
