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Researchers find 'surprising link' leads toward a new antibiotic
May 29, 2009McMaster University researchers have discovered a completely different way of looking for a new antibiotic
As the best drugs become increasingly resistant to superbugs, McMaster University researchers have discovered a completely different way of looking for a new antibiotic.
In a paper to be published published Friday, May 29 (embargo lifted 12 noon May 28) in the journal Chemistry and Biology, with colleagues in Germany and Wilfrid Laurier University, they report on work with the bacteria Staphylococcus aureus bacteria, the leading cause of infections in hospitals and the second most common community-acquired infection. Fewer and fewer antibiotics are effective against this bacteria.
Cell wall-active antibiotics, such as penicillin, kill bacteria by blocking production of the cell wall.
The researchers provide new evidence for genetic connections among three processes in the cell wall - teichoic acid, peptidoglycan and poly-isoprenoid synthesis. "Never before has such a profound link been drawn between these biosynthetic pathways supported by genetic, computational and biochemical evidence," they said in their paper.
"We found a connection that perhaps no one expected in the way the cell wall synthesis is wired," said lead author Eric Brown, professor and chair of the department of biochemistry and biomedical sciences in the Michael G. DeGroote School of Medicine.
"We found they are inextricably linked in their genetics and biochemistry," he said. "Along the way in this study, we have built a system that is ripe for being exploited as a way to search for small molecule drugs that would target these processes."
Potentially, he said, this may lead to the development of a new antibiotic.
Brown said the current arsenal of antibiotics was developed during the golden age of antibiotic drug discovery from 1930 to 1960, and then development stopped.
Research began again in earnest, he said, when troublesome strains of hospital and community-acquired infections began to emerge, such as MRSA (methicillin-resistant Staphylococcus aureus). "Since the 1960s, drug companies have for, the most part, been tweaking existing molecules, such as building better penicillin with minor changes to the original scaffold. But, you are not very far away from resistance when all you do is a little tweak."
The discovery of a "surprising link" between the three processes involved in cell wall synthesis lets researchers build a method of looking for molecules that will disturb the balance between them. "It offers a completely different way of looking for a new antibiotic that would be active against the cell wall," Brown said.
McMaster University
Cell wall-active antibiotics, such as penicillin, kill bacteria by blocking production of the cell wall.
The researchers provide new evidence for genetic connections among three processes in the cell wall - teichoic acid, peptidoglycan and poly-isoprenoid synthesis. "Never before has such a profound link been drawn between these biosynthetic pathways supported by genetic, computational and biochemical evidence," they said in their paper.
"We found a connection that perhaps no one expected in the way the cell wall synthesis is wired," said lead author Eric Brown, professor and chair of the department of biochemistry and biomedical sciences in the Michael G. DeGroote School of Medicine.
"We found they are inextricably linked in their genetics and biochemistry," he said. "Along the way in this study, we have built a system that is ripe for being exploited as a way to search for small molecule drugs that would target these processes."
Potentially, he said, this may lead to the development of a new antibiotic.
Brown said the current arsenal of antibiotics was developed during the golden age of antibiotic drug discovery from 1930 to 1960, and then development stopped.
Research began again in earnest, he said, when troublesome strains of hospital and community-acquired infections began to emerge, such as MRSA (methicillin-resistant Staphylococcus aureus). "Since the 1960s, drug companies have for, the most part, been tweaking existing molecules, such as building better penicillin with minor changes to the original scaffold. But, you are not very far away from resistance when all you do is a little tweak."
The discovery of a "surprising link" between the three processes involved in cell wall synthesis lets researchers build a method of looking for molecules that will disturb the balance between them. "It offers a completely different way of looking for a new antibiotic that would be active against the cell wall," Brown said.
McMaster University
Antibiotic Current Events and Antibiotic News RSSU.S. and European Experts Applaud Creation of New Transatlantic Task Force on Global Antibiotic Resistance Threat
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Teen girls diagnosed with STI more likely to seek treatment for partners after watching video
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UCLA researchers reconstitute enzyme that synthesizes cholesterol drug lovastatin
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Henry Ford Hospital study: A MRSA strain linked to high death rates
A strain of MRSA that causes bloodstream infections is five times more lethal than other strains and has shown to have some resistance to the potent antibiotic drug vancomycin used to treat MRSA, according to a Henry Ford Hospital study.
Bacteria 'launch a shield' to resist attack
Researchers from the University of Copenhagen and the Technical University of Denmark along with other collaborators in Denmark and the US found that the bacterium Pseudomonas aeruginosa can 'switch on' production of molecules that kill white blood cells - preventing the bacteria being eliminated by the body's immune system.
Pumpkin skin may scare away germs
The skin of that pumpkin you carve into a Jack-o'-Lantern to scare away ghosts and goblins on Halloween contains a substance that could put a scare into microbes that cause millions of cases of yeast infections in adults and infants each year.
Experts unveil new CVD guidelines and position papers
Several new guidelines and position papers offering the most up to date information to ensure that clinicians practice evidence-based medicine were released at the Canadian Cardiovascular Congress 2009 this week.
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