Using a laser device that allows them to view microscopic movement, biomedical engineering researchers at Johns Hopkins have produced startling new findings about how deadly bacteria spread infection between neighboring cells. Writing in the October 26 issue of Nature, Scot C. Kuo and James L. McGrath describe how Listeria monocytogenes--a common source of poisoning in processed foods--exhibit an unusual stutter-step motion while building rocketlike "tails" that propel them from one living host cell to another. The engineers' discovery contradicts a widely held belief that filaments in these tails grow and push in a smooth continuous motion.
To study the rocketlike motion of Listeria, the researchers used an innovative tracking device developed by Kuo. The instrument--a laser built into an optical microscope--allowed them to peer inside living cells and record the motion of Listeria microbes, the potentially fatal pathogens that have triggered a number of major processed food recalls in recent years.
Scientists already knew that Listeria evade detection by white blood cells--the body's key defense system--by hiding inside living intestinal cells. Inside each host cell, the pathogen feeds and multiplies until it causes the cell to burst and die. But before this happens, the bacteria causes molecules of a protein called actin to assemble into filaments to form rocketlike tails that can "thrust" bacteria from the infected cell toward a healthy neighboring cell. Scientists know that these filaments grow only near the bacterium but disassemble throughout the tail. The balance of growth and disassembly gives the appearance of a rocket "plume" of constant length.
Prior to beginning their project, Kuo and McGrath expected to confirm a theory that filament growth nudges a bacterium toward its next target in a smooth, continuous manner. Instead, Kuo and McGrath detected a series of steplike motions along the filaments. "We shouldn't have seen that. The fact that we can see these steplike motions means that the existing theories are missing a really fundamental feature," says Kuo, an assistant professor in the Department of Biomedical Engineering. His co-author, McGrath, is a postdoctoral fellow in his laboratory.
"Each bacterium is not just 'surfing' ahead of these tails as the filaments grow within the infected host cell," says Kuo. "Instead, the bacteria appear to hold onto some of these strands to control the locomotion process as new protein building blocks are incorporated into the tails. The steplike motion we observed could correspond to each addition of a building block."
The molecular-scale steps of Listeria are reminiscent of "motor" proteins, which haul "cargo" by a walking motion within cells. "Our data are the first indication that Listeria might use molecular motors," Kuo says.
Although their experiments focused on Listeria, Kuo and McGrath believe their findings also could shed light on the movement of related pathogens that cause ailments such as Rocky Mountain spotted fever, Shigella and vaccinia virus (a relative of smallpox).
Learning how these bacteria make use of their microscopic tails may not immediately lead to new treatments for these infections. But Kuo says these findings "add significantly to our basic understanding of how cells crawl and control their shape."