The mystery of how salmonella causes food poisoning is one step closer to being solved.
New research from the School of Medicine led by cell biology professor Dr. Jorge Galan, the chair of the section of microbial pathogenesis, has found that one of the infection’s biological mechanisms uses a series of proteins to gain control over human cells, facilitated by a syringe-like appendage which is created by the bacterium itself. The study, published online in the journal Science on Feb. 3, opens doors for the creation of a new class of antibiotics to combat salmonella, the leading cause of food poisoning in the United States, as well as the development of a novel method of vaccination that uses this mechanism.
The nano-syringe, embedded in the membrane of the bacterium, can inject proteins synthesized in the bacteria into the human cell, Galan said. Fifty to 70 varied proteins work together to turn the human cell into a “slave” of the bacteria, helping facilitate the bacteria’s replication process.
“It’s not like a brute-force entry through the cell, but rather it’s tricking the cell into taking the bacteria in,” he explained.
Maria Lara-Tejero GRD ’01, a postdoctoral fellow in Galan’s lab and the first author of the paper, said that the bacteria uses a specific recipe to form the syringe. First, a sorting platform forms on the surface of the cell’s cytoplasm that helps to line up the proteins that are used in the construction of the syringe, she explained. Then the human cell is punctured by the newly formed syringe and toxic bacterial proteins used to enslave the human cell are injected.
Samuel Wagner, a coauthor of the paper and a postdoctoral fellow in Galan’s lab, said he modified a common lab technique in order to see the complex.
“It’s really one of the bigger protein complexes that we know of,” he said, adding that this made the project difficult.
The study found that these proteins must be used in the appropriate order, or the complex loses its entire functionality, Galan said. It is this specific knowledge of the mechanism that could allow scientists to develop a more effective treatment against salmonella, he said.
Historically, antimicrobial agents have simply killed the bacteria, Galan said, but he said he hopes that drugs could be produced that are less blunt and specifically inhibit the bacteria’s method of attack.
Drugs that could inhibit the function of this syringe might also be exempt from the drug resistance induced by other types of antibiotics, Galan said. Scientists could use the study’s results to bioengineer the salmonella bacterium to insert specific proteins into the human cells.
“More on the applied side, we can engineer the machine to inject things that we want to deliver and that has been useful on the side of vaccines, for example,” he said, adding that his lab has conducted work using the nano-syringes to create vaccines against flu or cancer.
But Galan does not expect new developments from his research to materialize in the near future, he said.
“Every time in basic science you discover how something works doesn’t immediately materialize into a product or a drug to interfere with salmonella.”
The research was supported by a grant from the National Institutes of Health.