Researchers at the University of Texas Medical Branch (UTMB) are the first to use a combination of genomics and immunoinformatics approaches that could lead to vaccines against a dangerous bacterial pathogen commonly transmitted through contaminated beef. These findings are especially timely as new strains of the bacterium—known as Shiga-toxin producing E. coli (STEC) O157:H7—have been associated with more severe and lethal disease in humans. Results from the study were published in the March 2014 issue of Infection and Immunity.
STEC causes bloody diarrhea and may lead to other serious complications, including hemolytic uremic syndrome (HUS), the most common cause of acute kidney failure in children. The bacterial strain is responsible for approximately 0.9 cases per 100,000 people in the United States, and leads to a significant number of hospitalizations and deaths, particularly among children and the elderly.
“There is a real need to discover novel vaccine candidates against diarrheal diseases caused by pathogenic E. coli strains,” said lead study author Dr. Alfredo Torres of UTMB’s Department of Microbiology and Immunology. “Our approach helped identify several antigens specific to the O157 strain that we are using to develop an optimal vaccine.”
The research team studied the entire genome of the pathogen to identify specific proteins most likely to be effective as protective antigens, which stimulate the immune response from the body. They then refined their search using immunoinformatics to find the most promising candidates for vaccines.
The study was also the first to eliminate gene sequences found in commensal, or “beneficial” strains of E. coli that exist naturally in the human digestive tract, thus minimizing the risk that future vaccines based on these findings could affect these bacterial strains. Commensal E. coli strains aid in digestion and provide protection against pathogens.
Other authors of the paper (A comparative genomics and immunoinformatics approach for the identification of vaccine candidates for enterohemorrhagic Escherichia coli O157:H7) include Víctor A. García-Angulo, Anjana Kalita, Mridul Kalita at UTMB and Luis Lozano at Universidad Nacional Autónoma de México. This research was supported by funding from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.