Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel non-antibiotic agents against MRSA and common strep infections

13.09.2012
Drugs avoid antibiotic resistance trap by paralyzing bacteria instead of killing it, finds Case Western Reserve University researcher

Menachem Shoham, PhD, associate professor of biochemistry at Case Western Reserve University School of Medicine, has discovered novel antivirulence drugs that, without killing the bacteria, render Methicillin Resistant Staphylococcus Aureus (MRSA) and Streptococcus pyogenes, commonly referred to as strep, harmless by preventing the production of toxins that cause disease. The promising discovery was presented this week at the Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco.

MRSA infections are a growing public health concern, causing 20,000 to 40,000 deaths per year in the United States alone. It is the most prevalent bacterial pathogen in hospital settings and in the community at large, with about one million documented infections per year nationally, costing an estimated $8 billion annually to treat.

The problem has become increasingly severe as the bacteria have developed a resistance to antibiotics. As result, health care providers are running out of options to treat patients suffering from antibiotic-resistant infections, like MRSA and strep, 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," says Dr. Shoham. "We have discovered potential antivirulence drugs that block the production of toxins, thus rendering the bacteria harmless. Contrary to antibiotics, these new antivirulence drugs do not kill the bacteria. 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 turning on 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 libraries of many thousands of "drug-like" compounds and finding out which compounds would fit best into the activation site on AgrA. Subsequently, about 100 of the best scoring compounds were 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 so-called "lead" compounds.

Optimization of the initial "lead" compounds was performed by chemical synthesis of 250 new compounds bearing small but important chemical modifications on one of the initial leads. More than a dozen active compounds have been discovered by this method. The best drug candidate reduces red blood cell rupture by 95 percent without affecting bacterial growth.

Beginning this fall, Dr. Shoham and colleagues will begin testing the drug candidate in animal models.

"It is possible to inhibit virulence of MRSA without killing the bacteria," continues Dr. Shoham. "Such antivirulence drugs may be used for prophylaxis or therapy by themselves or in combination with an antibiotic. Antivirulence therapy may resensitize bacteria to antibiotics that have become ineffective by themselves."

This research was carried out in the laboratory of Dr. Menachem Shoham; funding was provided by grants from the Steris Corp., based in Mentor, Ohio, and the American Heart Association.

About Case Western Reserve University School of Medicine

Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes -- research and scholarship, clinical mastery, leadership, and civic professionalism -- to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.

Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report, "Guide to Graduate Education."

The School of Medicine's primary affiliate is University Hospitals Case Medical Center and is affiliated additionally with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu.

Jessica Studeny | EurekAlert!
Further information:
http://www.case.edu

More articles from Health and Medicine:

nachricht Using fragment-based approaches to discover new antibiotics
21.06.2018 | SLAS (Society for Laboratory Automation and Screening)

nachricht Scientists learn more about how gene linked to autism affects brain
19.06.2018 | Cincinnati Children's Hospital Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>