Shigellosis Biology and Genetics

Basic research helps scientists better understand how food- and water-borne microbes cause disease in humans.

NIAID supports research to study how bacterial pathogens (germs) cause disease when they infect, colonize, and then interact with the human host's body. For example, scientists have discovered that some bacteria can recognize that they are inside the intestinal tract and then activate an important set of their genes that enable them to live in the body and cause disease. Other NIAID-sponsored research focuses on how the organism grows and interacts inside the human cell. Scientists have identified genes that permit Shigella to obtain iron, an essential nutrient, from the human body. In addition, scientists have identified genes that appear to be involved in signaling certain immune system cells to cause inflammation, which may contribute to the development of diarrhea. Investigators are further defining the ways by which the toxins produced by Shigella result in the kidney damage leading to hemolytic uremic syndrome (HUS), a life-threatening condition. The primary goal of this research is to better understand how this kidney disease progresses. Future studies like these might define new ways to intervene, whether by prevention or treatment, in the disease process.

Recently, scientists have determined the complete genome sequences (genetic blueprint) for Shigella flexneri, as well as other major enteric bacteria. Scientists hope that sequencing information will speed the discovery of new targets for treatments and vaccines against foodborne pathogens.

NIAID-supported researchers are investigating small molecules that inhibit bacterial components that are critical for the development of shigellosis; these small molecules act through novel mechanisms that hopefully will not lead to the emergence of drug resistance that can occur with the use of antibiotics. Small molecules currently under study act to limit damage to the intestine, to prevent bacteria from obtaining essential nutrients, and to prevent the transport of bacterial proteins to the bacterial cell surface where they interact with the host cell in a variety of ways to cause disease.

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