Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
BioConferenceLive
JIB

Study Finds Bacterial Antigen Critical in Lethal Effects of Infection, Provides Clues for Therapy

By BiotechDaily International staff writers
Posted on 27 Aug 2013
A predominant molecular cause underlying lethal forms of infective endocarditis, sepsis, and kidney damage that often result from Staphylococcus aureus infection has been found, as well as indications for prevention and treatment therapies.

According to a study by a collaborative team at the University of Iowa (Iowa City, Iowa, USA) and the University of Minnesota (Minneapolis, MN, USA), the major superantigen (SAg) produced by S. aureus, staphylococcal enterotoxin C (SEC), is also a major cause of these severe conditions. Using the methicillin-resistant S. aureus (MRSA) strain MW2, the team showed that lethal sepsis, infective endocarditis and acute kidney infections in rabbits are critically dependent on high-level SAgs. SAgs, particularly SEC, were found to have a critical role in the development of all three conditions and that the association results from both superantigenicity and direct toxic effects on endothelial cells, the latter likely contributing to delayed endothelium healing. In contrast, the isogenic strain lacking SEC was found to be attenuated in virulence, and complementation with SEC restores disease production.

Infective endocarditis resulting from staph infection has a mortality rate of about 40%–50%, and about half of the surviving patients will suffer a stroke. The study showed that SEC not only over activates the immune system, but that this “excessive immune response is actually contributing very significantly to the destructive aspects of the disease, including capillary leakage, low blood pressure, shock, fever, destruction of the heart valves, and strokes that may occur in half of patients," said Patrick Schlievert, PhD, professor and chair of microbiology at the UI Carver College of Medicine. In addition to effects of excessive immune response, the SAgs also appear to have direct toxic effects, in part via endothelial cell stimulation.

Treatment therapeutics and prevention by vaccination are potential strategies for blocking these harmful effects. "We have high affinity molecules that neutralize superantigens and we have previously shown in experimental animals that we can actually prevent strokes associated with endocarditis in animal models. Likewise, we have shown that we can vaccinate against the superantigens and prevent serious disease in animals," said Prof. Schlievert. Also, low blood flow via the infection site appears to be one of the consequences of SEC’s action. The team found that increasing blood pressure by fluid replacement therapy reduced the formation of vegetations (the plaque-like meshwork made up of bacteria and host cell factors) on the heart valves and significantly protected from infective endocarditis, possibly also by washing away significant amounts of the superantigen molecule itself.

The study was published online August 20, 2013, in the American Society for Microbiology journal mBio.

Related Links:

University of Iowa
University of Minnesota
US National Institutes of Health



comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: Microcomputed tomography images (top) and histology images (bottom) of the knees of mice fed a very high fat diet containing omega-3 fatty acid supplement (left) or only omega-6 fatty acids (right) after a knee injury. The omega-6 diet showed abnormal bone remodeling and calcified tissue formation in the joint (white arrow). The omega-6 diet also showed significant loss of cartilage (red staining, yellow arrowhead) and increased joint inflammation (Photo courtesy of Duke University).

Dietary Omega-3 Fatty Acids Moderate Severity of Osteoarthritis in a Mouse Model

Researchers working with an osteoarthritis (OA) obese mouse model found that the fat content of the animals' diet contributed more to the development or arrest of OA than did body weight.... Read more

Therapeutics

view channel

Vaccine Being Developed for Heart Disease Close to Reality

The world’s first vaccine for heart disease is becoming a possibility with researchers demonstrating significant arterial plaque reduction in concept testing in mice. Klaus Ley, MD, from the La Jolla Institute for Allergy and Immunology (LA Jolla, CA, USA), and a vascular immunology specialist, is leading the vaccine... Read more

Business

view channel

A Surge in IPOs Revitalize Investments for the Global Pharma and Biotech

Anti-infective drugs, oncology, and pharmaceutical contract laboratories attract the most investment up to now. The intensified private equity and venture capital (PEVC) deal activity in the global healthcare industry during the recession years, 2008–2010, witnessed a waning post-2010. However, the decline in deals... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.