Public release date: 12-Sep-2012 [ | E-mail | Share ]

Contact: Jessica Studeny jessica.studeny@case.edu 216-368-4692 Case Western Reserve University

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.

More:
Novel non-antibiotic agents against MRSA and common strep infections

BYU biochemistry professor Emily Bates has made recent discoveries that may revolutionize medicine

BYU research has shed light on the cause and prevention of birth defects as well as cancer.

BYU biochemistry professor Emily Bates and a few of her students recently preformed and published research that may lead to a permanent answer for birth defects and impact how cancer is treated.

Fetal Alcohol Syndrome anda rare condition called Andersen-Tawil Syndrome both cause birth defects like cleft palates, small or missing teeth andmisshapedor connected fingers and toes. Andersen-Tawil Syndrome is caused by genetic changes in a potassium channel, which is also the same channel blocked by consumption of alcohol.

Bates and her students made the revolutionary discovery that potassium channels help cells receive instructions that tell them what they are and where they should be.

Dr. Bates in the research lab

The instructions for cells to divide and move need to be sent during pregnancy while a baby is developing, but those signals should turn off after the baby is born so the cells stay where they are. In cancer cells, the signal has turned back on, allowing cells to metastasize or invade other tissues and allow for growth of new tumors.

Not only are Bates and her students excited to have found some information about the causes of Andersen-Tawil and Fetal Alcohol Syndrome, they are also excited to test a possible therapy to stop the spread of cancer cells throughout the body.

What happens later on in life if someone gets cancer, is that this pathway turns on when its not supposed to turn on anymore, Bates said. The cancer cells start to metastasize, or invade another tissue causing more tumors. What we hope is that blocking this channel will block a signaling pathway that drives metastasis.

In other words, if Bates and her students can eventually find a way to block the channel after it opens back up, cancer cells will not spread throughout the body once the original tumor is removed.

More here:
BYU breakthrough targets birth defects - BYU biochemistry professor Emily Bates has made recent discoveries that may ...

Editor's Choice Main Category: Genetics Also Included In: Biology / Biochemistry Article Date: 12 Sep 2012 - 11:00 PDT

Current ratings for: Sex Can Cause Genetic Changes In Women

5 (1 votes)

A team of researchers from the University of East Anglia set out to determine the response female fruit flies (Drosophila melanogaster) have to mating.

The findings, published in Proceedings of the Royal Society B, indicated that semen consists of a single protein which generates a variety of responses in numerous genes in females, which appears evident at different instances and in different areas of their bodies after mating.

The discovery in the flies, the authors suggest, may be similar to responses in many animals, where semen is inserted into the female's body while having sex.

According to research earlier this year in PLoS Biology, neurodegenerative disorders that occur in both fruit flies and humans are caused by mutations in the same gene, showing that it is plausible that humans may experience the same effect during sex that fruit flies do with the activation of genes.

Scientists have been aware that males pass on seminal fluid proteins to their partner while mating, impacting their feeding, sleep patterns, immunity, egg laying, sexual receptivity, and water balance.

Professor Tracey Chapman, from UEA's school of Biological Sciences and head author, said:

Researchers identified significant changes to genes linked to:

Go here to see the original:
Sex Can Cause Genetic Changes In Women

Public release date: 12-Sep-2012 [ | E-mail | Share ]

Contact: Jessica Studeny jessica.studeny@case.edu 216-368-4692 Case Western Reserve University

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.

View post:
Novel non-antibiotic agents against MRSA and common strep infections

BYU biochemistry professor Emily Bates has made recent discoveries that may revolutionize medicine

BYU research has shed light on the cause and prevention of birth defects as well as cancer.

BYU biochemistry professor Emily Bates and a few of her students recently preformed and published research that may lead to a permanent answer for birth defects and impact how cancer is treated.

Fetal Alcohol Syndrome anda rare condition called Andersen-Tawil Syndrome both cause birth defects like cleft palates, small or missing teeth andmisshapedor connected fingers and toes. Andersen-Tawil Syndrome is caused by genetic changes in a potassium channel, which is also the same channel blocked by consumption of alcohol.

Bates and her students made the revolutionary discovery that potassium channels help cells receive instructions that tell them what they are and where they should be.

Dr. Bates in the research lab

The instructions for cells to divide and move need to be sent during pregnancy while a baby is developing, but those signals should turn off after the baby is born so the cells stay where they are. In cancer cells, the signal has turned back on, allowing cells to metastasize or invade other tissues and allow for growth of new tumors.

Not only are Bates and her students excited to have found some information about the causes of Andersen-Tawil and Fetal Alcohol Syndrome, they are also excited to test a possible therapy to stop the spread of cancer cells throughout the body.

What happens later on in life if someone gets cancer, is that this pathway turns on when its not supposed to turn on anymore, Bates said. The cancer cells start to metastasize, or invade another tissue causing more tumors. What we hope is that blocking this channel will block a signaling pathway that drives metastasis.

In other words, if Bates and her students can eventually find a way to block the channel after it opens back up, cancer cells will not spread throughout the body once the original tumor is removed.

See the rest here:
BYU breakthrough targets birth defects - BYU biochemistry professor Emily Bates has made recent discoveries that may ...