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Basic research is needed to better understand how the organisms that can be spread by contaminated food or water cause disease in humans. NIAID-supported researchers are studying the bacterial genes that play a role in colonization and pathogenesis of these organisms. For example, genes have been identified that appear to be involved in the signaling of immune system cells that cause inflammation, and which may contribute to the development of diarrhea. Other research sponsored by NIAID focuses on methods by which the organism grows and interacts in host cells. Scientists have discovered that some enteric bacteria recognize when they are in a human host and respond by activating a particular set of virulence genes that enable the organism to colonize the host and contribute to the disease process. Future studies will define new ways to intervene, whether by prevention or treatment, in the disease process.
In recent studies of EHEC and Shigella infections, NIAID-sponsored scientists have identified a gene in both types of bacteria that allows the organisms to resist the usually lethal effects of stomach acid. The great majority (85 percent, as shown in recent NIAID studies) of EHEC infections are caused by acid-resistant bacteria. The remaining 15 percent are caused by bacteria that have defects in a certain control gene common to all enteric bacteria. This gene turns on other genes and results in acid resistance. Isolating a gene that confers such a biological advantage is an important step toward improved treatment and prevention.
In other studies on EHEC, NIAID-sponsored investigators are further defining the mechanisms by which the toxins produced by EHEC and Shigella result in the kidney damage leading to hemolytic uremic syndrome. The primary goal of this research is to enhance understanding of physiological mechanisms underlying the progression of kidney vascular disease. Researchers are developing antitoxins that may be useful in preventing the development of hemolytic uremic syndrome in children who become infected. Researchers are also exploring vaccine approaches that would prevent EHEC and Shigella infections of animals or people.
Preliminary tests of live, attenuated Shigella flexneri vaccine candidates have resulted in the discovery of two new enterotoxins. Those toxins may contribute to the diarrhea associated with Shigella species. Studies are under way to elucidate the mechanism by which these toxins induce fluid loss. The findings will provide crucial information on how to improve attenuated vaccines to prevent shigellosis.
The NIAID enteric diseases program also supports basic and clinical research on Vibrio cholerae, Helicobacter pylori, Yersinia, Listeria, Clostridia, Bacteroides, Staphylococcus and enterotoxins.
NIAID supports an Enteric Pathogens Research Unit to carry out research on the mucosal immune response to infection with enteric pathogens. Because foodborne pathogens universally affect the intestinal mucosa, these studies will provide information needed to engineer vaccines or develop treatment for diseases caused by these organisms. The research includes clinical trials of vaccine candidates and the use of adjuvants, delivery systems, or dosing schedules that will help scientists determine how best to enhance the immune response to vaccines.
In addition to the organisms mentioned above, NIAID conducts research on other gastrointestinal pathogens such as Norwalk viruses, rotaviruses, and hepatitis A virus. Scientists at the NIAID Laboratory of Infectious Diseases devised the first method for detecting Norwalk virus particles and for measuring Norwalk virus-specific antibodies. They also developed a quadrivalent, live rotavirus vaccine for infants. Recent NIAID-supported clinical trials have shown this vaccine to be safe and 100 percent effective in preventing dehydrating disease or disease severe enough to require hospitalization. NIAID scientists also developed a recently licensed inactivated vaccine for hepatitis A virus infection.
As foodborne and waterborne diseases continue to have a major impact on health in the United States and elsewhere in the world, and with the emergence of drug-resistant strains of many organisms including Salmonella, biomedical research will continue to play a critical role in understanding the disease process, and in preventing and controlling these infections.
This information is not intended to be a substitute for professional medical advice. You should not use this material to diagnose or treat a health condition or disease without consulting with your healthcare provider.
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