Navigation Links
Case Western Reserve researcher discovers new 'anti-pathogenic' drugs to treat MRSA

CLEVELAND September 16, 2010 Menachem Shoham, PhD, associate professor and researcher in the department of biochemistry at the Case Western Reserve University School of Medicine, has identified new anti-pathogenic drugs that, without killing the bacteria, render Methicillin Resistant Staphylococcus Aureus (MRSA) harmless by preventing the production of toxins that cause disease.

Infections of MRSA are a growing public health problem causing 20,000 deaths per year in the U.S. alone. MRSA is the most prevalent bacterial pathogen in hospital settings and in the community at large. The problem has become increasingly severe due to the fact that the bacteria develop resistance to antibiotics. Currently, there are only two antibiotics available to treat MRSA (vancomycin and linezolid) and strains are emerging that are resistant even to these two remaining antibiotics. As result, healthcare providers are running out of options to treat patients suffering from antibiotic-resistant infections, creating a dire need for alternative treatments and approaches.

"Staph bacteria are ubiquitous and normally do not cause infections, however, occasionally these bacteria become harmful due to their secretion of toxins," said Dr. Shoham. "We have discovered potential "anti-pathogenic" drugs that block the production of toxins, thus rendering the bacteria harmless. Contrary to antibiotics, these new anti-pathogenic drugs do not kill the bacteria. And since the survival of the bacteria is not threatened by this approach, the development of resistance, like that to antibiotics, is not anticipated to be a serious problem."

Dr. Shoham identified a bacterial protein, known as AgrA, as the key molecule responsible for the release of toxins. AgrA, however, needs to be activated to induce toxin production. His goal was to block the activation of AgrA with a drug, thus preventing the cascade of toxin release into the blood that can lead to serious infections throughout the body.

The screening for AgrA inhibitors was initially carried out in a computer by docking a library of 90,000 compounds and finding out which compounds would fit best into the activation site on AgrA. Subsequently, about one hundred of the best scoring compounds were acquired and tested in the laboratory for inhibition of the production of a toxin that ruptures red blood cells.

Seven of these compounds were found to be active. Testing compounds bearing chemical similarity to the original compounds lead to the discovery of additional and more potent compounds.

More than a dozen active compounds have been discovered by this method. The best drug candidate reduces red blood cell rupture to 12% of the value without the drug at a concentration of 10 g/mL, without affecting bacterial growth..

"It is possible to inhibit virulence of MRSA without killing the bacteria," continued Dr. Shoham. "Such anti-pathogenic drugs may be used for prophylaxis or therapy by themselves or in combination with an antibiotic."

This research was carried out in the laboratory of Dr. Menachem Shoham in the Department of Biochemistry at the Case Western Reserve University School of Medicine in Cleveland, Ohio. Funding was provided by grants from the Steris Corporation and from the American Heart Association.

The results were presented at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston Conference Center earlier this week.


Contact: Christina DeAngelis
Case Western Reserve University

Related biology news :

1. Case Western Reserve geneticist receives prestigious NIH Directors Pioneer Award
2. Pancreatic cancers use fructose, common in the Western diet, to fuel their growth
3. UT Southwestern researchers find key step in bodys ability to make red blood cells
4. Case Western Reserve awarded $4.7 million from Defense Advanced Research Projects Agency
5. UT Southwestern researchers use novel sperm stem-cell technique to produce genetically modified rats
6. Temperature and salt levels of the Western Mediterranean are on the increase
7. UT Southwestern researchers find mechanism that may stop E. coli from developing in cattle
8. UT Southwestern researchers identify key molecular step to fighting off viruses
9. Case Western Reserve team discovers smart insulin molecule
10. UT Southwesterns BioCenter driving biotech, medical innovation in North Texas
11. New brain nerve cells key to stress resilience, UT Southwestern researchers find
Post Your Comments:
(Date:11/2/2015)... PARK, Calif. , Nov. 2, 2015  SRI ... $9 million to provide preclinical development services to the ... the contract, SRI will provide scientific expertise, modern testing ... wide variety of preclinical pharmacology and toxicology studies to ... --> The PREVENT Cancer Drug Development ...
(Date:10/29/2015)... -- Connected health pioneer, Joseph C. Kvedar , MD, ... and wellness, and the business opportunities that arise from ... of Healthy Things . Long before health and ... Kvedar, vice president, Connected Health, Partners HealthCare, was creating ... from the hospital or doctor,s office into the day-to-day ...
(Date:10/27/2015)... 27, 2015 Synaptics Inc. (NASDAQ: SYNA ), ... Google has adopted the Synaptics ® ClearPad ® ... power its newest flagship smartphones, the Nexus 5X by ... --> --> Synaptics works ... strategic collaboration in the joint development of next generation ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... -- Studies reveal the differences in species ... the way for more effective treatment for one of the ... --> --> Gum disease ... cats, yet relatively little was understood about the bacteria associated ... conducted by researchers from the WALTHAM Centre for Pet Nutrition ...
(Date:11/25/2015)... 2015 Orexigen® Therapeutics, Inc. (Nasdaq: OREX ... fireside chat discussion at the Piper Jaffray 27th Annual ... The discussion is scheduled for Wednesday, December 2, at ... A replay will be available for 14 days after ... Julie NormartVP, Corporate Communications and Business Development , BrewLife(858) ...
(Date:11/24/2015)... , Nov. 24, 2015 Cepheid (NASDAQ: ... be speaking at the following conference, and invited investors ... York, NY      Tuesday, December 1, 2015 at ... York, NY      Tuesday, December 1, 2015 at ... Healthcare Conference, New York, NY ...
(Date:11/24/2015)... 2015 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ:  AEZS) (TSX: AEZ) ... of the Toronto Stock Exchange, confirms that as of ... corporate developments that would cause the recent movements in ... --> About Aeterna Zentaris Inc. ... Aeterna Zentaris is a specialty biopharmaceutical company engaged ...
Breaking Biology Technology: