Researchers from UTHealth Medical School revealed a “molecular secretion machine” from the bacterium Shigella flexneri crucial for host infection and important for the development of potential anti-bacterial drugs to prevent infection and disease. The study entitled “Visualization of the type III secretion sorting platform of Shigella flexneri” was published in the Proceedings of the National Academy of Sciences.
The gram-negative bacterium Salmonella is estimated to affect 1.2 million people in the United States, with 19,000 hospital internalizations and 380 deaths. The most common symptoms due to salmonella are diarrhea, fever and abdominal cramps occurring within 12 to 72 hours after infection, accordingly to the Centers for Disease Control and Prevention. Shigella, a gram-negative bacterium, rod-shaped bacteria very closely related to Salmonella, is estimated to cause 80 to 165 million cases of disease and 600,000 deaths annually across the globe. Shigella flexneri is one of four shigella species. Several pathogenic bacteria, such as Shigella and Salmonella, use type III secretion machines, also called injectisomes, similar to a hypodermic needle, to transfer virulence proteins into eukaryotic host cells.
For the first time, the research team combined advanced imaging, using a microscope capable of zooming in on very small organisms on the scale of billionths of a meter, and genetic techniques to visualize the frozen-hydrated diarrheal pathogen Shigella flexneri and disclose the intact type III secretion machine and its interaction with a host cell. The characterization of these structures may provide novel insights into the mechanisms involved in type III secretion and pathogenesis and also emphasize the main evolutional distinctions within this bacterial flagellum.
“It was like Google Earth in that you are able to zoom in on tiny molecular machines. But unlike Google Earth in which many of the streets and boulevards are already known, we were charting new areas and making new maps. You could call it cartography,” said Morado, an UTHealth research assistant.
Dr. William Margolin, co-author of the study, said that the characterization of the secretion machine structure may help in the identification of potential drug targets.