Navigation Links
Anthrax inhibitor counteracts toxin, may lead to new therapeutics

Researchers from Rensselaer Polytechnic Institute and the University of Toronto have designed a nanoscale assembly of molecules that successfully counteracts and inhibits anthrax toxin in animal and laboratory experiments. The novel approach used to neutralize anthrax toxin could be applied in designing potent therapeutics for a variety of pathogens and toxins, according to the researchers.

Anthrax toxin, secreted by the anthrax bacterium, is made of proteins and toxic enzymes that bind together to inflict damage on a host organism. The inhibitor, which is described by the Rensselaer-Toronto team in the April 23 online edition of the journal Nature Biotechnology, works by preventing the assembly of toxic enzyme components, thereby blocking the formation of fully assembled anthrax toxin and neutralizing its activity.

The inhibitor protected rats from anthrax toxin in the study.

"Our eventual goal is to use the inhibitor as a human therapeutic for anthrax exposure, one that can stop the toxin from functioning inside the body," says Ravi Kane, the Merck Associate Professor of Chemical and Biological Engineering at Rensselaer and a principal investigator of the project. "Combining the inhibitor with antibiotic therapy may increase the likelihood of survival for an infected person."

The 2001 intentional release of anthrax spores via postal mail in the United States led to increased research on possible therapeutics and vaccines to treat toxins that could be used as biological weapons. The current treatment for anthrax exposure is antibiotics, but inhalation anthrax still has a fatality rate of 75 percent even after antibiotics are given, according to the Centers for Disease Control and Prevention. Antibiotics slow the progression of infection by targeting the bacteria, but do not counter the advanced destructive effects of anthrax toxin in the body.

Anthrax toxin is a polyvalent protein complex in that it displays multiple copies of identical binding surfaces on the same structure. The inhibitor designed by the Rensselaer-Toronto team is also polyvalent and recognizes these surface patterns on the anthrax toxin molecular structure, allowing it to bind at multiple sites and become four orders of magnitude more potent than an inhibitor that binds to a single site.

"Think about how two Lego blocks snap together. A brick with four studs can interlock with a brick with four holes. These bricks will grip together better than if they had only one stud and one hole," says Jeremy Mogridge, Canada Research Chair and assistant professor of Laboratory Medicine and Pathobiology at the University of Toronto. "Furthermore, Lego works because the pattern of studs on one brick matches the pattern of holes on another."

Earlier work by other groups has shown that an inhibitor with a fixed pattern of chemical groups can recognize a protein with a similar fixed pattern of complementary groups. In this study, the team demonstrated that a therapeutic inhibitor displaying random patterns can recognize a target if its statistical characteristics match those of the toxin target. According to the researchers, endowing inhibitors with statistical pattern-matching capabilities is less difficult than designing inhibitors with fixed structures.

"The pattern matching-based approach used by our research team to neutralize anthrax toxin should be broadly applicable in designing potent therapeutics for a variety of pathogens and toxins, including influenza and HIV," says Kane.

The researchers tested their pattern-matching strategy by designing a polyvalent inhibitor for cholera toxin, demonstrating that this approach also could be used successfully to enhance the potency of polyvalent inhibitors directed to this target and, they suggest, others. They note the work also could be useful for creating specific target recognition in biological sensors.

The team says their work demonstrates fo r the first time that liposome-based polyvalent inhibitors are effective in animals and they are continuing development on the anthrax inhibitor through additional animal testing.


'"/>

Source:Rensselaer Polytechnic Institute


Related biology news :

1. Study Models Impact Of Anthrax Vaccine
2. Anthrax test, developed by army and CDC, receives FDA approval
3. Anthrax inhibitors identified by Burnham team
4. Anthrax stops body from fighting back, study shows
5. Anthrax spores may survive water treatment
6. Anthrax attack posed greater potential threat than thought
7. Anthrax paralyzes immune cells with lethal toxin, UF research shows
8. Protease inhibitors reach beyond HIV
9. UNC scientists discover new role for protein as fundamental inhibitor of cell movement
10. Small molecule inhibitor of cholera discovered
11. Enzyme inhibitors block replication of SARS virus
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:1/25/2016)... 25, 2016  Glencoe Software, the world-leading supplier of ... industries, will provide the data management solution OMERO Plus ... Photo - ... Phenotypic analysis measures the characteristics and ... comparisons between states such as health and disease, the ...
(Date:1/20/2016)... , Jan. 20, 2016   MedNet Solutions , ... entire spectrum of clinical research, is pleased to announce ... significant achievements are the result of the company,s laser ... iMedNet eClinical , it,s comprehensive, easy-to-use and highly ... --> Key MedNet growth achievements in 2015 ...
(Date:1/13/2016)... , January 13, 2016 /PRNewswire/ ... announced the addition of the  "India ... Estimation & Forecast (2015-2020)"  report ... http://www.researchandmarkets.com/research/7h6hnn/india_biometrics ) has announced the addition ... Identification Market - Estimation & Forecast ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... , Feb. 11, 2016  Spectra BioPharma Selling ... (CSO) that provides biopharma companies the experience, expertise, ... and deploy outsourced sales teams. Created in concert ... addresses both the strategic and tactical needs of ... sales solutions through both personal and non-personal promotion. ...
(Date:2/11/2016)... BioInformant announces the February 2016 release of its ... and Technologies – Market Size, Segments, Trends, and Projections ... The first and only market research firm ... more than a decade of historical information on all ... type. This powerful 175 page global strategic report contains ...
(Date:2/10/2016)... WASHINGTON , February 10, 2016 Early-career ... , Peru , Uganda ... their life-enhancing work in health and nutrition   Indonesia ... Uganda and Yemen are ... sciences and epidemiology. They are also celebrated for mentoring young women scientists ...
(Date:2/10/2016)... (NYSE MKT: ISR), a medical technology company and innovator ... treatment of prostate, brain, lung, head and neck and ... second quarter and six months of fiscal 2016, which ... --> Revenue was $1.19 million for ... 31, 2015, a 12% increase compared to $1.07 million ...
Breaking Biology Technology: