Researchers discover a molecule's previously unknown role in fighting off E. coli
“At the most fundamental levels, it gives us new insights into the way in which our host immune response engages and enables protection mechanisms at that portal of entry. From a therapeutic standpoint, better understanding of these pathways will enable researchers to explore ways to therapeutically manipulate the immune response to prevent and eradicate infectious pathogens at these critical body sites.”
While the study, “HVEM signaling at mucosal barriers provides host defense against pathogenic bacteria,” focused on E. coli and pneumococcus (also known as Streptococcus pneumoniae), Dr. Kronenberg said the HVEM mechanism is likely involved in protecting the body from many other dangerous bacteria and other microorganisms. In fact, HVEM stands for herpes virus entry mediator, and it is a protein that herpes virus uses to enter cells.
In the study, the researchers used mice genetically engineered not to have HVEM. When these mice were exposed to pneumococcus or a mouse pathogen very similar to E. coli, the HVEM deficiency led to a much greater susceptibility to infection, higher bacterial burdens and significantly compromised the mucosal barrier. “It is striking how similar the responses in the lung and the intestine were,” said Dr. Kronenberg. “The mice without HVEM were unable to respond effectively at either site, and the deficit was not only major but also nearly immediate, within two days of exposure to the microorganisms.”
“In the present era of ever increasing antibiotic resistance, innovative approaches to treatment of bacterial infections are urgently needed,” commented Victor Nizet, M.D., a professor of Pediatrics and Pharmaceutical Sciences at the University of California San Diego. “These importantly include new approaches to strengthen immune resistance to infection, and the discovery by the La Jolla Institute scientists reveals HVEM as a candidate drug target with relevance to multiple pathogens and multiple sites of infection.”
The release notes that pneumococcus is the most common cause of bacterial pneumonia and meningitis in children. According to the World Health Organization (WHO), pneumonia is the single largest cause of death in children worldwide, annually killing an estimated 1.4 million children under the age of five. While cases among U.S. children have declined significantly due to the introduction of a pneumococcal vaccine in 2000, the bacteria remains a significant problem, particularly among U.S. children under two years, the elderly and throughout the developing world.
Escherichia coli (abbreviated as E. coli) are a large and diverse family of bacteria. Although most strains of E. coli are harmless, some can be deadly. E. coli creeps into the food supply through contamination by tiny (usually invisible) amounts of human or animal feces. Many people may develop mild symptoms, but some suffer severe complications that can lead to kidney failure and death. In 2011 an E. coli outbreak centered in Germany sickened more than 4,000 people, ultimately killing fifty people in fifteen countries. The outbreak was eventually traced to contaminated bean sprouts.
— Read more in Jr-Wen Shui et al., “HVEM signalling at mucosal barriers provides host defence against pathogenic bacteria,” Nature (15 July 2012) (doi:10.1038/nature11242)
