Disease-causing microbes like the food-borne bacterium Listeria monocytogenes specialize in invading and replicating inside their animal hosts' own cells, making them particularly tricky to defeat. Now, a new study led by biologists at the University of California, Berkeley, has identified a molecular alarm system in which the intracellular pathogen sends out signals that kick the immune response into gear.
The findings, to be reported the week of July 14 in the journal Proceedings of the National Academy of Sciences, shed light on how the cells recognize and destroy the pathogenic bugs living within their walls, and may even provide new targets for the research and development of new vaccines and drugs.
The pathogens' signals come from multidrug resistance transporters (MDRs), membrane proteins used by a wide variety of organisms to pump out a broad range of molecules from their systems. Similar transporters have been linked in other studies to the development of resistance to multiple drugs that are toxic to the pathogen. This study is the first to connect multidrug resistance transporters directly to stimulation of the immune system, although the nature of the molecules that the bacteria are spitting out remains unclear.
"For the MDRs to work, the pathogen needs to be alive, so this study actually shows how the immune system can tell the difference between a living, harmful microbe and one that is dead," said the study's principal investigator, Daniel Portnoy, a UC Berkeley professor with joint appointments in the Department of Molecular and Cell Biology and the School of Public Health, and associate director of the Berkeley Center for Emerging and Neglected Diseases. "This is important because you don't want the immune system to overreact to non-threats, which is what happens in autoimmune disorders such as inflammatory bowel disease, asthma and multiple sclerosis."
The Listeria bacterium makes headlines when it contaminates deli meats, raw cheeses, cole slaw and other foods. According to the Centers for Disease Control and Prevention, Listeria causes some 2,500 infections and 500 deaths each year, and at greatest risk are people who have weakened immune systems or are pregnant.
The bacteria first trick immune cells into swallowing them, where they become encased in bubbles called vacuoles. The bacteria become dangerous when they break out of these bubbles into the cells' internal fluid, or cytosol, to multiply and spread the infection. The role of MDRs is not clearly known, but the results of this study plainly show that one particular MDR transporter is necessary for the host to respond to the infection, the authors said. In addition, overexpression of this or other related MDRs leads to an enhanced host immune response.
"The only way the bug molecule enters into the cytosol is if the bacterium is virulent," said Portnoy, who is also a member of UC Berkeley's Health Sciences Initiative. "We know that there are different immune system receptors in different compartments of a cell, but until this paper, it was not understood exactly how the cytosolic surveillance system was triggered. Our findings suggest that the molecules pumped out by the pathogen while it's in the cellular fluid help the immune system gauge whether a bacterium is a threat based upon its location inside the cell."
The researchers isolated the role of multidrug resistance transporters by manipulating specific genes in the bacteria that controlled their expression and then measuring how increased or decreased activity by the transporter proteins impacted levels of interferon beta, a protein produced by the immune system that rally more disease-fighting cells when infections are detected.
They found that greater MDR expression led to greater stimulation of the immune system, as measured by interferon beta levels.
Strains of Listeria with higher levels of MDR expression increased interferon beta levels up to 20-fold compared with unmodified, wild-type Listeria in cell cultures, the study found. Tests in mice infected with those same mutant strains of Listeria had bacterial loads that were 20 times lower in their livers, although the researchers could not attribute the decreased levels solely to the higher levels of interferon beta.
"This paper raises the classic issue of the tug-of-war in the evolution of the host and the pathogen; it's a never-ending arms race," said Gregory Crimmins, UC Berkeley graduate student in molecular and cell biology who, along with former UC Berkeley post-doctoral researcher Anat Herskovits, was the study's co-lead author.
The study results could provide clues to the actions of other intracellular pathogens, such as the bacteria responsible for tuberculosis and Legionnaires' disease, since they also activate similar immune mechanisms, the researchers said.
Crimmins noted that better understanding of how the class of interferons in this study is triggered could have implications for a variety of diseases. "Type I interferons have wide-ranging effects on the immune system, and are used to treat multiple sclerosis, hepatitis C and some types of cancer," he said. "The strains generated in this study may provide novel insight into the role of Type I interferons in coordinating the host immune response."
"By understanding the pathways of innate immunity, we can better understand acquired immunity, and that is important for vaccine development," added Portnoy. "The concept of making safe but fully effective vaccines is still a challenge, especially for intracellular pathogens."
Portnoy pointed out that weakened Listeria is already being used to develop cancer vaccines by Anza Pharmaceuticals, a Concord-based biopharmaceutical company with which he consults.
Source : University of California - Berkeley
Sunday, August 24, 2008
A viral cloaking device
Viruses achieve their definition of success when they can thrive without killing their host. Now, biologists Pamela Bjorkman and Zhiru Yang of the California Institute of Technology have uncovered how one such virus, prevalent in humans, evolved over time to hide from the immune system.
The human immune system and the viruses hosted by our bodies are in a continual dance for survival--viruses ever seek new ways to evade detection, and our immune system devises new methods to hunt them down. Human Cytomegalovirus (HCMV), says Bjorkman, Caltech's Delbrück Professor of Biology and a Howard Hughes Medical Institute (HHMI) Investigator, "is the definition of a successful virus--it thrives but it doesn't affect the host."
HCMV is carried by eight in 10 people. Although it generally harms only those who are immunocompromised, it has also been linked with brain tumors like the one for which Ted Kennedy recently had surgery. Understanding how HCMV survives may help in the development of a vaccine, as well as in the fight against other viruses with similar evasive tactics.
"We are interested in mechanisms taken by viruses to escape our immune system," says Caltech biology postdoc and HHMI associate Zhiru Yang. She and Bjorkman published their findings on HCMV survival mechanisms in the July 15 edition of Proceedings of the National Academy of Sciences. They describe the underpinnings of a viral cloaking device, partly made of stolen goods from healthy cells, that helps HCMV to move undetected through the body.
For 20 years, Bjorkman's lab has been dedicated to understanding class 1 major histocompatibility complex (MHC) proteins and the immune response, most recently related to AIDS research. MHC proteins carry peptides, small pieces that are chopped up from the cell's internal proteins, to the cell's surface. If a cell has been infected, MHC presents viral peptides to signal T cells to kill it. So some viruses evolved to evade T cells by keeping MHC from reaching the cell surface. In turn, the immune system recruited other hunters to search for cells that don't show MHC proteins.
Sometime along its treacherous evolutionary path, HCMV stole a class 1 MHC molecule from its host and modified it for supreme stealth. "This is a decoy," Bjorkman says. She and Yang analyzed the structure of the mimic, called UL18, to compare how similar it is to the real thing. They found that despite a mere 23 percent match in genetic sequences, UL18 looks almost exactly the same as a true class 1 MHC.
The same immune cells that search for missing MHC proteins are designed to bind to them when they find them, thereby inhibiting an immune response. Yang and Bjorkman found that UL18 happens to bind 1,000 times tighter to these inhibitory receptors than real MHC molecules do. "This is exactly what the virus wants--to avoid being recognized by T cells, but to engage inhibitory receptors to turn off immune cells," Yang notes. "Only a small number of UL18 molecules are required to have the same inhibitory effect as a large number of MHC class I molecules."
"What I find astounding is that the virus stole this gene and kept it almost identical but improved upon its binding," Bjorkman says.
UL18 didn't stop there. "It also binds peptides--that's unique to this MHC mimic. We don't know why," Bjorkman adds. The peptide is obscured from killer cells by yet another shield, Yang says. In a trait it shares with HIV proteins, HCMV's UL18 covers itself with carbohydrates, which are unrecognizable to the immune system. A real class 1 MHC molecule has one site for adding carbohydrates; the fake has 13, Bjorkman notes. The only place where it's not covered is where it binds to the inhibitory receptor.
All its efforts have made UL18 virtually undetectable. "It's a good example of a viral protein that evolved from its host ancestor to block unwanted interactions," Yang says. "The more we understand that, the more effectively we can fight viruses that hide out," Bjorkman adds.
Source : California Institute of Technology
The human immune system and the viruses hosted by our bodies are in a continual dance for survival--viruses ever seek new ways to evade detection, and our immune system devises new methods to hunt them down. Human Cytomegalovirus (HCMV), says Bjorkman, Caltech's Delbrück Professor of Biology and a Howard Hughes Medical Institute (HHMI) Investigator, "is the definition of a successful virus--it thrives but it doesn't affect the host."
HCMV is carried by eight in 10 people. Although it generally harms only those who are immunocompromised, it has also been linked with brain tumors like the one for which Ted Kennedy recently had surgery. Understanding how HCMV survives may help in the development of a vaccine, as well as in the fight against other viruses with similar evasive tactics.
"We are interested in mechanisms taken by viruses to escape our immune system," says Caltech biology postdoc and HHMI associate Zhiru Yang. She and Bjorkman published their findings on HCMV survival mechanisms in the July 15 edition of Proceedings of the National Academy of Sciences. They describe the underpinnings of a viral cloaking device, partly made of stolen goods from healthy cells, that helps HCMV to move undetected through the body.
For 20 years, Bjorkman's lab has been dedicated to understanding class 1 major histocompatibility complex (MHC) proteins and the immune response, most recently related to AIDS research. MHC proteins carry peptides, small pieces that are chopped up from the cell's internal proteins, to the cell's surface. If a cell has been infected, MHC presents viral peptides to signal T cells to kill it. So some viruses evolved to evade T cells by keeping MHC from reaching the cell surface. In turn, the immune system recruited other hunters to search for cells that don't show MHC proteins.
Sometime along its treacherous evolutionary path, HCMV stole a class 1 MHC molecule from its host and modified it for supreme stealth. "This is a decoy," Bjorkman says. She and Yang analyzed the structure of the mimic, called UL18, to compare how similar it is to the real thing. They found that despite a mere 23 percent match in genetic sequences, UL18 looks almost exactly the same as a true class 1 MHC.
The same immune cells that search for missing MHC proteins are designed to bind to them when they find them, thereby inhibiting an immune response. Yang and Bjorkman found that UL18 happens to bind 1,000 times tighter to these inhibitory receptors than real MHC molecules do. "This is exactly what the virus wants--to avoid being recognized by T cells, but to engage inhibitory receptors to turn off immune cells," Yang notes. "Only a small number of UL18 molecules are required to have the same inhibitory effect as a large number of MHC class I molecules."
"What I find astounding is that the virus stole this gene and kept it almost identical but improved upon its binding," Bjorkman says.
UL18 didn't stop there. "It also binds peptides--that's unique to this MHC mimic. We don't know why," Bjorkman adds. The peptide is obscured from killer cells by yet another shield, Yang says. In a trait it shares with HIV proteins, HCMV's UL18 covers itself with carbohydrates, which are unrecognizable to the immune system. A real class 1 MHC molecule has one site for adding carbohydrates; the fake has 13, Bjorkman notes. The only place where it's not covered is where it binds to the inhibitory receptor.
All its efforts have made UL18 virtually undetectable. "It's a good example of a viral protein that evolved from its host ancestor to block unwanted interactions," Yang says. "The more we understand that, the more effectively we can fight viruses that hide out," Bjorkman adds.
Source : California Institute of Technology
New evidence of battle between humans and ancient virus
For millennia, humans and viruses have been locked in an evolutionary back-and-forth -- one changes to outsmart the other, prompting the second to change and outsmart the first. With retroviruses, which work by inserting themselves into their host's DNA, the evidence remains in our genes. Last year, researchers at Rockefeller University and the Aaron Diamond AIDS Research Center brought an ancient retrovirus back to life and showed it could reproduce and infect human cells. Now, the same scientists have looked at the human side of the story and found evidence that our ancestors fought back against that virus with a defense mechanism our bodies still use today.
"This is the first time that we've been able to take an ancient retrovirus and analyze how it interacts with host defense mechanisms in the laboratory in the present day," says Paul Bieniasz, who is an associate professor and head of the Laboratory of Retrovirology at Rockefeller and a scientist at the Aaron Diamond AIDS Research Center. Bieniasz and graduate student Youngnam Lee took their resurrected virus, called HERV-K, tested its strength against molecules involved in human antiviral defense and published their results in the Journal of Virology (online ahead of print, June 18).
Bieniasz, who also is an investigator at the Howard Hughes Medical Institute, and Lee found that, at least in the laboratory, human cells infected with HERV-K fought back with several antiviral proteins. One of those proteins, called APOBEC3G, leaves a tell-tale signature behind: It mutates virus DNA in a recognizable pattern and is one our cells use to attack modern retroviruses. "But this is the first time it's been shown for this ancient retrovirus," Bieniasz says.
Once the scientists found that modern human cells attacked HERV-K with this molecule, they went back to look at the "fossil evidence," remnants of the virus that still remain in our genes and that the researchers had previously used to reconstruct it. What emerged were two copies of HERV-K that had clearly been mutated, and thus inactivated, by the APOBEC3G protein. "We're looking at things that happened millions and millions of years ago," says Lee. "But these sorts of ancient interactions may have influenced how humans are able to combat these retroviruses today. These proteins help protect us against current retroviruses." Indeed, HERV-K may well have helped to shape the modern APOBEC3G defense.
The earlier study and this one provide two sides of the evolutionary coin: the infectious agent, and the host defense. "Retroviruses are able to infect us and leave remnants in our DNA, and our DNA also holds evidence of what we've done to them in return," Lee says. "It's an illustration of the fight between host and virus."
Source : Rockefeller University
"This is the first time that we've been able to take an ancient retrovirus and analyze how it interacts with host defense mechanisms in the laboratory in the present day," says Paul Bieniasz, who is an associate professor and head of the Laboratory of Retrovirology at Rockefeller and a scientist at the Aaron Diamond AIDS Research Center. Bieniasz and graduate student Youngnam Lee took their resurrected virus, called HERV-K, tested its strength against molecules involved in human antiviral defense and published their results in the Journal of Virology (online ahead of print, June 18).
Bieniasz, who also is an investigator at the Howard Hughes Medical Institute, and Lee found that, at least in the laboratory, human cells infected with HERV-K fought back with several antiviral proteins. One of those proteins, called APOBEC3G, leaves a tell-tale signature behind: It mutates virus DNA in a recognizable pattern and is one our cells use to attack modern retroviruses. "But this is the first time it's been shown for this ancient retrovirus," Bieniasz says.
Once the scientists found that modern human cells attacked HERV-K with this molecule, they went back to look at the "fossil evidence," remnants of the virus that still remain in our genes and that the researchers had previously used to reconstruct it. What emerged were two copies of HERV-K that had clearly been mutated, and thus inactivated, by the APOBEC3G protein. "We're looking at things that happened millions and millions of years ago," says Lee. "But these sorts of ancient interactions may have influenced how humans are able to combat these retroviruses today. These proteins help protect us against current retroviruses." Indeed, HERV-K may well have helped to shape the modern APOBEC3G defense.
The earlier study and this one provide two sides of the evolutionary coin: the infectious agent, and the host defense. "Retroviruses are able to infect us and leave remnants in our DNA, and our DNA also holds evidence of what we've done to them in return," Lee says. "It's an illustration of the fight between host and virus."
Source : Rockefeller University
Yale researchers uncover West Nile's targets
Screening the entire human genome, a team headed by Yale University scientists have identified several hundred genes that impact West Nile virus infection. The findings reported Wednesday online in the journal Nature may give scientists valuable new clues about ways to intervene in a host of deadly viral infections.
"Diseases like West Nile affect millions of people," said Erol Fikrig, professor of medicine and microbial pathogenesis at Yale, an investigator with the Howard Hughes Medical Institute, and senior author of the paper. "We have found a dictionary of genes critical to a viral infection. Using these techniques, this can be done with any virus."
West Nile is transmitted by mosquitoes and has become a significant health threat in many parts of the United States since being introduced into North America in 1999. Symptoms range from mild flu-like symptoms to potentially fatal inflammation of the brain and central nervous system. West Nile is part of the flavivirus family, which includes dengue, yellow fever and tick- borne encephalitis viruses, among others, and causes thousands of deaths annually.
West Nile virus consists of only 10 proteins so it must hijack dozens of cellular processes of the host in order to infect individuals and replicate. To find out exactly which of those processes were involved in an infection, the team from Yale and three other research instituitions used a technique called global RNA interference targeting strategy.
Using tiny snippets of small interfering RNA, scientists are now able to disable individual genes and thereby assess their function. Testing the entire human genome, the team was able to identify 305 individual proteins that can alter viral infection. Many of those proteins appear crucial to the ability of the virus to infect people and reproduce. About 30 percent of the genes involved in West Nile infection also appear to play a role in Dengue fever, the researchers report.
Theoretically, if scientists can find a way to interfere in the virus' ability to use those proteins it might be possible to treat or prevent a variety of different infections. "It might be possible to find a 'pan flavivirus' target," Fikrig said.
Source : Yale University
"Diseases like West Nile affect millions of people," said Erol Fikrig, professor of medicine and microbial pathogenesis at Yale, an investigator with the Howard Hughes Medical Institute, and senior author of the paper. "We have found a dictionary of genes critical to a viral infection. Using these techniques, this can be done with any virus."
West Nile is transmitted by mosquitoes and has become a significant health threat in many parts of the United States since being introduced into North America in 1999. Symptoms range from mild flu-like symptoms to potentially fatal inflammation of the brain and central nervous system. West Nile is part of the flavivirus family, which includes dengue, yellow fever and tick- borne encephalitis viruses, among others, and causes thousands of deaths annually.
West Nile virus consists of only 10 proteins so it must hijack dozens of cellular processes of the host in order to infect individuals and replicate. To find out exactly which of those processes were involved in an infection, the team from Yale and three other research instituitions used a technique called global RNA interference targeting strategy.
Using tiny snippets of small interfering RNA, scientists are now able to disable individual genes and thereby assess their function. Testing the entire human genome, the team was able to identify 305 individual proteins that can alter viral infection. Many of those proteins appear crucial to the ability of the virus to infect people and reproduce. About 30 percent of the genes involved in West Nile infection also appear to play a role in Dengue fever, the researchers report.
Theoretically, if scientists can find a way to interfere in the virus' ability to use those proteins it might be possible to treat or prevent a variety of different infections. "It might be possible to find a 'pan flavivirus' target," Fikrig said.
Source : Yale University
Early treatment is key to combating hepatitis C virus
Canadian researchers have shown that patients who receive early treatment for Hepatitis C virus (HCV) within the first months following an infection, develop a rapid poly-functional immune response against HCV similar to when infection is erradicted spontaneously, according to a new study published in the Journal of Virology. Therefore, early treatment can restore immune response against HCV and help eliminate the virus rapidly. This new discovery of the mechanisms of viral eradication could contribute to the development of new treatments.
About a quarter of infected individuals eradicate the infection spontaneously, without treatment. Led by Dr. Naglaa Shoukry and Dr. Julie Bruneau, affiliated to both the Research Centre of the Université de Montréal Hospital Centre and the Université de Montréal, as well as with researchers from the Institut national de la santé et de la recherché scientifique (Montréal branch), the study found that early treatment restores a rapid poly-functional immune response, characterized by the simultaneous production of multiple antiviral mediators.
HCV is transmitted through infected blood. Although a quarter of infected patients can eradicate the infection spontaneously, the majority develop persistent infection, a major cause of cirrhosis and cancer of the liver. The only approved treatment for HCV is an anti-viral drug known as pegylated interferon alpha. This drug is successful in only half of cases when administered during chronic infection. Success rates among those treated early after infection are significantly higher or around 90%.
In North America alone, most new HCV infections occur among intravenous drug users (IDUs), a vulnerable population that is often undiagnosed and untreated. In the study, researchers followed a group of IDUs at high risk of HCV infection before and immediately after exposure to HCV. Their findings clearly show the importance of early diagnosis and treatment of HCV – particularly in marginalized populations such as IDUs and aboriginal populations.
Source : University of Montreal Hospital Centre
About a quarter of infected individuals eradicate the infection spontaneously, without treatment. Led by Dr. Naglaa Shoukry and Dr. Julie Bruneau, affiliated to both the Research Centre of the Université de Montréal Hospital Centre and the Université de Montréal, as well as with researchers from the Institut national de la santé et de la recherché scientifique (Montréal branch), the study found that early treatment restores a rapid poly-functional immune response, characterized by the simultaneous production of multiple antiviral mediators.
HCV is transmitted through infected blood. Although a quarter of infected patients can eradicate the infection spontaneously, the majority develop persistent infection, a major cause of cirrhosis and cancer of the liver. The only approved treatment for HCV is an anti-viral drug known as pegylated interferon alpha. This drug is successful in only half of cases when administered during chronic infection. Success rates among those treated early after infection are significantly higher or around 90%.
In North America alone, most new HCV infections occur among intravenous drug users (IDUs), a vulnerable population that is often undiagnosed and untreated. In the study, researchers followed a group of IDUs at high risk of HCV infection before and immediately after exposure to HCV. Their findings clearly show the importance of early diagnosis and treatment of HCV – particularly in marginalized populations such as IDUs and aboriginal populations.
Source : University of Montreal Hospital Centre
Thursday, August 21, 2008
'We may never get rid of our hospital superbugs'
Thursday August 21 2008
HOSPITAL bugs like MRSA and C Diff -- linked to dozens of deaths in Ireland -- may always be with us, a top consultant has warned.
C Diff infection contributed to 10 deaths at St Colmcille's Hospital, Loughlinstown last year, and to 13 deaths at Ennis General Hospital.
A new virulent strain of C Diff, called 027, has emerged recently and it has more toxins in it than in other types of C Diff, making it a more serious strain, consultant microbiologist with the Health Protection Surveillance Centre, Dr Fidelma Fitzpatrick said.
The priority was to minimise the incidence of Healthcare-Associated Infections (HCAIs) as much as possible and she believed hospitals have procedures in place to prevent them.
But eventually eliminating MRSA, C Diff and other infections in hospitals or the community is problematic because "as long as there is healthcare, there will be HCAIs," she said.
High risk patients include those who are older, have a damaged immune system due to cancer or other diseases, patients on antibiotics or those with breaks in their skin from insertion of drips, from wounds or burns or after surgery.
C Diff is a bug found in the bowel of about one in 20 healthy patients and is kept in check by the "good" bacteria in the bowel.
"If a patient takes an antibiotic, sometimes this can kill off the good bacteria in the bowel and that allows bugs such as C Diff to multiply and in some patients this can also lead to C Diff infection," Dr Fitzpatrick said.
The most common symptom of C Diff is diarrhoea, although some people complain of nausea, reduced appetite and crampy abdominal pain.
"It's important to remember that most patients recover completely from C Diff," she said.
"However, in a small percentage of patients, the infection causes an inflammation of the bowel (colitis) and that can be very serious. But again, it is more serious in the high risk groups of patients."
The most recent comprehensive study, in 2006, showed that approximately one in 20 Irish patients had a HCAI at the time of the study. The incidence was less than in England, where around one in 12 patients had a HCAI at the time.
- Source: - Harold.ie
HOSPITAL bugs like MRSA and C Diff -- linked to dozens of deaths in Ireland -- may always be with us, a top consultant has warned.
C Diff infection contributed to 10 deaths at St Colmcille's Hospital, Loughlinstown last year, and to 13 deaths at Ennis General Hospital.
A new virulent strain of C Diff, called 027, has emerged recently and it has more toxins in it than in other types of C Diff, making it a more serious strain, consultant microbiologist with the Health Protection Surveillance Centre, Dr Fidelma Fitzpatrick said.
The priority was to minimise the incidence of Healthcare-Associated Infections (HCAIs) as much as possible and she believed hospitals have procedures in place to prevent them.
But eventually eliminating MRSA, C Diff and other infections in hospitals or the community is problematic because "as long as there is healthcare, there will be HCAIs," she said.
High risk patients include those who are older, have a damaged immune system due to cancer or other diseases, patients on antibiotics or those with breaks in their skin from insertion of drips, from wounds or burns or after surgery.
C Diff is a bug found in the bowel of about one in 20 healthy patients and is kept in check by the "good" bacteria in the bowel.
"If a patient takes an antibiotic, sometimes this can kill off the good bacteria in the bowel and that allows bugs such as C Diff to multiply and in some patients this can also lead to C Diff infection," Dr Fitzpatrick said.
The most common symptom of C Diff is diarrhoea, although some people complain of nausea, reduced appetite and crampy abdominal pain.
"It's important to remember that most patients recover completely from C Diff," she said.
"However, in a small percentage of patients, the infection causes an inflammation of the bowel (colitis) and that can be very serious. But again, it is more serious in the high risk groups of patients."
The most recent comprehensive study, in 2006, showed that approximately one in 20 Irish patients had a HCAI at the time of the study. The incidence was less than in England, where around one in 12 patients had a HCAI at the time.
- Source: - Harold.ie
MicuRx Pharmaceuticals Selects Next-Generation Antibiotic Candidate Targeting MRSA and Expands Operation in China
MicuRx Pharmaceuticals, Inc., a privately-held biopharmaceutical company developing next-generation antibiotics, today announced the nomination of MRX- I as its first preclinical development candidate. MRX-I is an antibacterial molecule targeting multi-drug resistant gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Simultaneously, the company expanded its operations in China to increase MicuRx' capacity in antibacterial drug discovery and development.
"Only 12 months after initial funding, we have discovered multiple drug leads and selected our first development candidate MRX-I, a promising antibacterial compound that we expect to be superior to many of the top- selling antibiotics available today," said Zhengyu Yuan, Ph.D., president and chief executive officer of MicuRx Pharmaceuticals, Inc. "This enhanced productivity is owed in part to our hybrid business model that leverages the drug discovery capacity readily available in China and the superior management expertise in the United States."
"MRX-I and additional MicuRx pipeline leads have been identified using our proprietary drug discovery platform," commented Mike F. Gordeev, Ph.D., executive vice president and chief scientific officer of MicuRx. "We will continue to leverage this novel platform to further enhance the pharmacological properties and safety profile of clinically validated antibiotic classes, creating best-in-class antibiotics capable of addressing the growing problem of the bacterial multi-drug resistance."
MicuRx raised $10 million in 2007 with Morningside Group as the sole investor. To facilitate the development of its lead compounds and expand the research capacity, MicuRx recently moved its research and development operations in China to a new 10,000 square-foot facility in ZhangJian HighTech Park in Shanghai, China. The company intends to use this integrated state-of- art chemistry and biology facility for drug discovery and development activities to advance its next-generation antimicrobial products.
About Multi-Drug Resistance and MRSA
Modern antimicrobials (antibiotics and related pharmaceuticals) have substantially reduced the threat posed by infectious diseases and contributed to a dramatic drop in mortality rates over the past 30 years. However, due to widespread use of existing drugs in the community and hospital environment, pathogenic bacteria resistant to current antimicrobial therapies have evolved and become ubiquitous, presenting a global health threat. The World Health Organization has set forth a mandate to combat this growing problem and encouraged an urgent action of the member countries. MicuRx is addressing this need directly by developing best-in-class antimicrobials targeting multi- drug resistant bacteria.
About MicuRx Pharmaceuticals, Inc.
MicuRx is discovering and developing next-generation antibacterial and antifungal products. By applying designer modifications to validated antibiotics, MicuRx intends to improve overall pharmacological properties of antimicrobial drugs in order to overcome antibiotic resistance, increase the antibacterial spectrum, improve the dosing regimen, or reduce adverse side effects. The company has research and development facilities in San Francisco Bay Area and ZhangJiang High-Tech Park in Shanghai, China.
CONTACT: Zhengyu Yuan, Ph.D., President and CEO of MicuRx Pharmaceuticals,Inc., +1-510-324-8662, ; or Angela Bitting,+1-925-202-6211, , for MicuRx Pharmaceuticals, Inc. zyuan@micurx.com a.bitting@comcast.net
"Only 12 months after initial funding, we have discovered multiple drug leads and selected our first development candidate MRX-I, a promising antibacterial compound that we expect to be superior to many of the top- selling antibiotics available today," said Zhengyu Yuan, Ph.D., president and chief executive officer of MicuRx Pharmaceuticals, Inc. "This enhanced productivity is owed in part to our hybrid business model that leverages the drug discovery capacity readily available in China and the superior management expertise in the United States."
"MRX-I and additional MicuRx pipeline leads have been identified using our proprietary drug discovery platform," commented Mike F. Gordeev, Ph.D., executive vice president and chief scientific officer of MicuRx. "We will continue to leverage this novel platform to further enhance the pharmacological properties and safety profile of clinically validated antibiotic classes, creating best-in-class antibiotics capable of addressing the growing problem of the bacterial multi-drug resistance."
MicuRx raised $10 million in 2007 with Morningside Group as the sole investor. To facilitate the development of its lead compounds and expand the research capacity, MicuRx recently moved its research and development operations in China to a new 10,000 square-foot facility in ZhangJian HighTech Park in Shanghai, China. The company intends to use this integrated state-of- art chemistry and biology facility for drug discovery and development activities to advance its next-generation antimicrobial products.
About Multi-Drug Resistance and MRSA
Modern antimicrobials (antibiotics and related pharmaceuticals) have substantially reduced the threat posed by infectious diseases and contributed to a dramatic drop in mortality rates over the past 30 years. However, due to widespread use of existing drugs in the community and hospital environment, pathogenic bacteria resistant to current antimicrobial therapies have evolved and become ubiquitous, presenting a global health threat. The World Health Organization has set forth a mandate to combat this growing problem and encouraged an urgent action of the member countries. MicuRx is addressing this need directly by developing best-in-class antimicrobials targeting multi- drug resistant bacteria.
About MicuRx Pharmaceuticals, Inc.
MicuRx is discovering and developing next-generation antibacterial and antifungal products. By applying designer modifications to validated antibiotics, MicuRx intends to improve overall pharmacological properties of antimicrobial drugs in order to overcome antibiotic resistance, increase the antibacterial spectrum, improve the dosing regimen, or reduce adverse side effects. The company has research and development facilities in San Francisco Bay Area and ZhangJiang High-Tech Park in Shanghai, China.
CONTACT: Zhengyu Yuan, Ph.D., President and CEO of MicuRx Pharmaceuticals,Inc., +1-510-324-8662, ; or Angela Bitting,+1-925-202-6211, , for MicuRx Pharmaceuticals, Inc. zyuan@micurx.com a.bitting@comcast.net
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